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Several selective androgen receptor modulators (SARMs) have been synthesized and investigated in humans, rats, and dogs in the past, but no data are yet available concerning the metabolism of SARMs in horses. The aryl-propionamide-derived drug candidates S24 and S4 (andarine) have a strong androgen receptor binding affinity and show distinctive specific cell answers. Although no SARM drug candidate (aiming for testosterone replacement therapy) has completed clinical trials yet, S4 has been illicitly available via the Internet. These facts led to the prohibition of SARMs by the German equestrian federation, and the (mis)use of such compounds would further represent a doping rule violation in horse racing. In this study, the drug candidates S24 and S4 were subjected to in vitro metabolism experiments with equine liver microsomal preparations from a female Quarter Horse to obtain information about potential target analytes in equine doping control analysis. The enzymatically synthesized metabolites were characterized by liquid chromatography–tandem mass spectrometry and –high-resolution/high-accuracy mass spectrometry. All observed S24 and S4 equine metabolites are in agreement with earlier in vitro and in vivo studies in humans and dogs. Nevertheless, the relative percentage of generated equine metabolites (as determined from the analytes’ response in full-scan chromatography–tandem mass spectrometry and –high-resolution/high-accuracy mass spectrometry measurements) differs considerably from the reported profiles. Although the S24 metabolite pattern is comparably balanced concerning glucuronidated and sulfonated conjugates, the major S4 metabolite was found to be the unconjugated dephenylated compound, with a proportion of more than 90%.  相似文献   
24.
Leptin: a possible metabolic signal affecting reproduction   总被引:8,自引:0,他引:8  
Since its discovery in 1994, leptin, a protein hormone synthesized and secreted by adipose tissue, has been shown to regulate feed intake in several species including sheep and pigs. Although a nimiety of information exists regarding the physiological role of leptin in rodents and humans, the regulation and action of leptin in domestic animals is less certain. Emerging evidence in several species indicates that leptin may also affect the hypothalamo-pituitary-gonadal axis. Leptin receptor mRNA is present in the anterior pituitary and hypothalamus of several species, including sheep. In rats, effects of leptin on GnRH, LH and FSH secretion have been inconsistent, with leptin exhibiting both stimulatory and inhibitory action in vivo and in vitro. Evidence to support direct action of leptin at the level of the gonad indicates that the leptin receptor and its mRNA are present in ovarian tissue of several species, including cattle. These leptin receptors are functional, since leptin inhibits insulin-induced steroidogenesis of both granulosa and thecal cells of cattle in vitro. Leptin receptor mRNA is also found in the testes of rodents. As with the ovary, these receptors are functional, at least in rats, since leptin inhibits hCG-induced testosterone secretion by Leydig cells in vitro. During pregnancy, placental production of leptin may be a major contributor to the increase in maternal leptin in primates but not rodents. However, in both primates and rodents, leptin receptors exist in placental tissues and may regulate metabolism of the fetal-placental unit. As specific leptin immunoassays are developed for domestic animals, in vivo associations may then be made among leptin, body energy stores, dietary energy intake and reproductive function. This may lead to a more definitive role of leptin in domestic animal reproduction.  相似文献   
25.
本文介绍了蛋氨酸的功能,并且详细阐述了蛋氨酸的代谢过程和吸收过程,为合理调控蛋氨酸在动物体内的吸收代谢和在饲料中添加蛋氨酸提供了理论依据。  相似文献   
26.
Summary

This study was initiated to investigate the influence of a daily dose of anionic salts (AS) above the valid upper limit at present on metabolism of dairy cows. Eleven non‐pregnant and non‐lactating Holstein‐Friesian crossbred cows with a permanent rumen cannula were used in a study with a controlled feeding design. The initial daily dose was 2500 meq/day, which resulted in a Dietary Cation Anion Difference (DCAD) of ‐211 meq/kg dry matter. Every seven days, the daily dose was raised by 500 meq. If a cow stopped eating, the application of AS was stopped and these cows were monitored over the next seven days. On day 30 another batch of hay, having the same DCAD but higher concentrations of minerals and energy, was fed. Blood and urine samples were taken to monitor acid‐base balance and calcium concentrations. Acid‐base balance was strongly influenced by AS. Blood pH dropped steadily and reached values around 7.23. Urine pH dropped quickly below 6 and remained at that level regardless of the increased dosage of AS. Net acid base excretion (NABE) fell continuously with the increase of the dosage of AS and reached values below ‐200 mmol/l. Calcium concentrations in the serum were nearly stable, but those in urine increased sharply and remained on an elevated level with increasing doses of AS. A few days before the individual cow's refusal of feed intake, calcium excretion in urine decreased. The majority of cows stopped eating while consuming a diet containing 3500 to 4000 meq AS except two animals who consumed up to 6000 meq/day AS but they received the better hay in the second half of the treatment period. In this time pH in blood increased slowly. NABE remained stable on a low level at ‐100 mmol/l. The results showed that with an increasing amount of AS fed the risk of clinical acidosis increased. The decreasing urine concentrations of calcium indicate a breakdown of the compensation capability of the single cow. Besides the dose of AS fed, the quality of the feed stuff might be another factor concerning the tolerance of cows against AS.  相似文献   
27.
Liu C  Liang YR  Zheng XQ 《茶叶》2013,(4):240-246
Caffeine,theobromine and theophylline are the major purine alkaloids found in Camellia sinensis.Theacrine was detected in a special Chinese tea plant named kucha (Camellia kucha).With tracer experiments,the metabolism pathway of these purine alkaloids has mostly been explored.The isolation and cloning of the genes encoding enzymes in the related pathway made it possible to develop methods to control caffeine level in tea products via transgenic technique.Further study on the kucha species would be helpful to obtain materials for processing naturally caffeine-less tea.However,there is still a long way to go in this direction such as sensory improvement of products prepared using leaves of kucha.  相似文献   
28.
The synchronization and ovulatory responses of Sangsari cross bred ewes and metabolism of energy substrates in 8-cell stage embryos to hatched blastocysts stage produced in vitro or in vivo were investigated. Ewes were assigned randomly to receive 37.5 IU of porcine follicle stimulating hormone (FSH-P) daily for the 3 days preceding implant removal (Day 0). Synchronization of estrus was carried out using a 1.5 mg norgestomet (Crestar) ear implant for 12 days. Ewes in estrus were mated two to three times with rams of proven fertility. At the time of first mating each ewe was administered 1000 IU of human chorionic gonadotrophin (hCG) to induce ovulation. Surgical embryo recovery was performed on Days 4 and 6 after onset of estrus (Day 0) and recovered embryos were subjected to comparative metabolism studies with in vitro derived embryos at the same stage of development. The number of corpora lutea (CL), unovulated follicles and overall ovarian activity were recorded for each ewe during the breeding and non-breeding seasons. While the pattern of oxidation was similar among in vitro and in vivo derived embryos, a low pyruvate to lactate ratio was the preferred substrate of embryos derived in vitro. A high level of production of CO2 and lactate resulted from a stress response to the suboptimal culture environment. The first marked increase in the metabolism of glucose by ovine embryos was detected in compact morula stage, but there was no significant increase in the oxidation of glucose after the morula stage. Two different concentrations of glucose were compared, but this did not affect metabolism. However, the rate of incorporation and metabolism of glucose tended to be higher at the 0.56 mmol/L glucose dosage.  相似文献   
29.
一氧化氮信号途径参与草地早熟禾耐镉机制的研究   总被引:1,自引:0,他引:1  
鲜靖苹  王勇  马晖玲 《草地学报》2019,27(6):1577-1586
为探究信号分子一氧化氮(Nitric Oxide,NO)对镉(Cadmium,Cd)胁迫下草地早熟禾(Poa pratensis)的调控机理,揭示草地早熟禾耐镉机理,本试验采取根施1000 μmol·L-1氯化镉(Cadmium chloride hemidihydrate,CdCl2·2.5H2O)及叶面喷施NO合成酶抑制剂(L-硝基精氨酸甲酯(L-NAME))、硝酸还原酶抑制剂(钨酸钠(Tungstate))、NO清除剂(4-羧基苯-4,4,5,5-四甲基咪唑-1-氧-3-氧化物(cPTIO))处理草地早熟禾叶片,研究不同处理对草地早熟禾幼苗叶片生长及抗氧化酶活性、光合色素含量、丙二醛(Malondialdehyde,MDA)、游离脯氨酸、内源NO含量的影响。研究发现,镉胁迫下草地早熟禾内源NO含量增加,添加一氧化氮清除剂、一氧化氮合酶抑制剂、硝酸还原酶抑制剂可增加超氧化物歧化酶(Superoxide Dismutase,SOD)、过氧化氢酶(Catalase,CAT)、抗坏血酸过氧化物酶(Ascorbate peroxidase,APX)活性,降低过氧化物酶(Peroxidase,POD)活性,增加叶绿素a、叶绿素b、类胡萝卜素、丙二醛含量,降低脯氨酸(Proline,Pro)含量、叶片相对含水量(Relative Water Content,RWC)和干物质量(Dry matter content)。结果表明,一氧化氮合酶途径可能是早熟禾合成NO的主要途径,内源NO可通过调节抗氧化酶活性、光合色素含量、游离脯氨酸含量等途径缓解镉胁迫。  相似文献   
30.
Etoricoxib, a selective inhibitor of cyclooxygenase-2, is used in the treatment of many inflammatory diseases and dental pain in humans. The aim of this study was to determine the pharmacokinetics and metabolism of etoricoxib in horses. Six horses weighing an average of 475 ± 25 kg were administered a single oral dose of etoricoxib at 1 mg/kg body weight. The results show that the drug reached a maximum concentration of 505.2 ± 67.8 ng/mL in 48 minutes after administration. The elimination half-life was calculated to be 10.20 ± 1.30 hours. Mass spectrometric analysis confirmed that etoricoxib is metabolized in horses via the oxidation of its 6′-methyl group to form a hydroxyl methyl etoricoxib which can further be oxidized to form either an acid or be glucuronidated. In addition, the 1′-N terminal of 6′-hydroxymethyl metabolite is oxidized to form the corresponding 1′-N oxide metabolite. The present results have clearly demonstrated that etoricoxib is mainly excreted in urine as metabolites. From these data, it is also possible to postulate a detection time for the metabolites which in turn can assist in the control of illegal use of the drug in horse racing.  相似文献   
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