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Administration of a single large dose of ethanol to mice results in increases, for concentrations in the brain, of ratios of lactate to pyruvate, of aglycerophosphate to dihydroxyacetone phosphate, of malate to oxaloacetate, and of glutamate to the product of alpha-ketoglutarate and ammonium ion. These changes are noticed as early as 5 minutes after the single dose is given. Ethanol administration for 30 days also produces these changes in metabolite concentrations in the brain. However, in contrast to the single alcohol dose, long-term alcohol administration results in a marked decrease in the concentration of adenosine triphosphate in brain and increases in those of adenosine diphosphate and adenosine monophosphate. Pyrazole, an inhibitor of alcohol dehydrogenase, prevents the effects of ethanol on the concentration of brain metabolites. These results may provide new insight into the biochemical and pharmacological effects of alcohol on brain metabolism and the importance of alcohol dehydrogenase activity in the brain.  相似文献   
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The antifungal activity of ethylenediaminetetraacetic acid (EDTA) against Saccharomyces cerevisiae was significantly affected by various conditions such as inoculum size, pH, and metal ions (Mg(2+), Ca(2+)). EDTA was found to be effective against this yeast at the inoculum size of 10(5) colony forming units (CFU)/mL with the minimum inhibitory concentration of 400 mug/mL and the minimum fungicidal concentration of 6400 mug/mL, but it was not effective at 10(7) CFU/mL up to 6400 mug/mL. The fungicidal activity of EDTA against S. cerevisiae was significantly enhanced in combination with polygodial. Isobolograms, fractional inhibitory concentration, and fractional fungicidal concentration indices were used for evaluating the interaction between combined compounds. This synergistic effect is likely due to polygodial's destructive action on the cellular membrane, which facilitates the transmembrane transport of foreign compounds (EDTA) into yeast cells. Once inside the cells, EDTA forms chelation with divalent metals such as Mg(2+) and Ca(2+), which are required by various essential enzymes.  相似文献   
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Molecular design of antifungal agents   总被引:3,自引:0,他引:3  
In a rational approach to the design of antifungal agents against Saccharomyces cerevisiae, a series of alkyl gallates (3,4,5-trihydroxybenzoates) were synthesized and assayed. Nonyl gallate (1) was found to be the most effective with a minimum fungicidal concentration (MFC) of 12.5 microg/mL (42 microM), followed by octyl gallate (2) with an MFC of 25 microg/mL (89 microM). These MFCs are little influenced by pH values. A time-kill curve study indicates that nonyl gallate exhibits fungicidal activity against S. cerevisiae at any growing stage. The antifungal activity of nonyl gallate is due primarily to its ability to act as a nonionic surface-active agent (surfactant). The length of the alkyl group is not a major contributor but plays a role in eliciting the activity to a large extent. As far as alkyl gallates are concerned, their antimicrobial spectra and potency depend largely on the hydrophobic portion of the molecules.  相似文献   
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A series of aliphatic (2E)-alkenals from C(5) to C(14) were tested for their antifungal activity against Saccharomyces cerevisiae ATCC 7754. (2E)-Undecenal (C(11)) was found to be the most effective with the minimum fungicidal concentration (MFC) of 6.25 microgram/mL, followed by (2E)-decenal (C(10)) with an MFC of 12.5 microgram/mL. The time-kill curve study showed that (2E)-undecenal was fungicidal against S. cerevisiae at any growth stage, and this activity was not influenced by pH values. The (2E)-alkenals inhibited glucose-induced acidification by inhibiting the plasma membrane H(+)-ATPase. The primary antifungal action of medium-chain (C(9)-C(12)) (2E)-alkenals against S. cerevisiae comes from their ability to function as nonionic surface-active agents (surfactants), disrupting the native membrane-associated function nonspecifically. Hence, the antifungal activity of (2E)-alkenals is mediated by biophysical processes, and the maximum activity can be obtained when the balance between the hydrophilic and hydrophobic portions becomes the most appropriate.  相似文献   
79.
The gamma-aminobutyric acid (GABA) receptor bears sites of action for insecticides. To discover GABA receptor-directed insecticides in natural products, fungal culture extracts were screened for their ability to inhibit specific binding of the radiolabeled noncompetitive antagonist [3H]1-(4-ethynylphenyl)-4-n-propyl-2,6,7-trioxabicyclo[2.2.2]octane to housefly head membranes. The screening efforts led to the isolation of two alkaloids from Aspergillus terreus: PF1198A (alantrypinone) and PF1198B (serantrypinone), which had IC50 values of 0.34 and 2.1 microM, respectively, in this assay. These compounds were ca. 47-61-fold selective for housefly vs rat GABA receptors. Both compounds showed insecticidal activity against Myzus persicae in the range of 100-500 ppm. Binding assay-guided screening should provide significant opportunities for the identification of novel and selective insecticides.  相似文献   
80.
The degradation of spiked anthracene (ANT), pyrene (PYR) and benzo[a]pyrene (B[a]P) in soil (3000 mg ∑ 3 PAHs kg−1 dry soil) was studied in aerobically incubated microcosms for 120 d. The applied treatments aimed at enhancing PAH removal from the heavily contaminated soils are: (i) bioaugmentation by adding aged PAH-contaminated soil (ACS) containing activated indigenous degraders; and (ii) combined bioaugmentation/biostimulation by incorporating sewage sludge compost (SSC) and decaying rice straw (DRS). The adopted treatments produced higher PAH dissipation rates than those observed in unamended PAH-spiked soils, especially for ANT and PYR in the presence of DRS or ACS (>96%). However, B[a]P was the most recalcitrant hydrocarbon to biodegradation. Extracellular enzyme investigation revealed the existence of ligninolytic activities in all soil treatments, including control but no relationship could be found with PAH dissipation. The ecotoxicological assessment indicated that regardless of applied treatment, PAH-spiked soils were chronically lethal to ostracod Heterocypris incongruens and confirmed the sensitivity of the microcrustacean to the concomitant presence of these three hydrocarbons. Lettuce root elongation inhibition was correlated with PAH level but the presence of SSC conferred a strong phytotoxic capacity to PAH-spiked soils. DRS amendment may constitute a cost-effective alternative for hydrocarbon bioremediation as it has impacted positively on soil microbial activity and enhanced PAH removal with no apparent changes in soil physico-chemical properties.  相似文献   
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