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The modes of binding of adenosine 2'-monophosphate (2'-AMP) to the enzyme ribonuclease (RNase) T1 were determined by computer modelling studies. The phosphate moiety of 2'-AMP binds at the primary phosphate binding site. However, adenine can occupy two distinct sites--(1) The primary base binding site where the guanine of 2'-GMP binds and (2) The subsite close to the N1 subsite for the base on the 3'-side of guanine in a guanyl dinucleotide. The minimum energy conformers corresponding to the two modes of binding of 2'-AMP to RNase T1 were found to be of nearly the same energy implying that in solution 2'-AMP binds to the enzyme in both modes. The conformation of the inhibitor and the predicted hydrogen bonding scheme for the RNase T1-2'-AMP complex in the second binding mode (S) agrees well with the reported x-ray crystallographic study. The existence of the first mode of binding explains the experimental observations that RNase T1 catalyses the hydrolysis of phosphodiester bonds adjacent to adenosine at high enzyme concentrations. A comparison of the interactions of 2'-AMP and 2'-GMP with RNase T1 reveals that Glu58 and Asn98 at the phosphate binding site and Glu46 at the base binding site preferentially stabilise the enzyme-2'-GMP complex. 相似文献
3.
Conformations of several high-mannose-type oligosaccharidesthat are generated during the biosynthetic degradation of Man9GlcNAc2to Man5GlcNAc2 have been studied by molecular dynamics (MD).Simulations were performed on NCI-FCRDC's Cray Y-MP 8D/8128supercomputer using Biosym's CVFF force field for 1000 Ps withdifferent initial conformations. The conformations of the two1,3- and the two 1,6-linkages in each oligomannose were different,suggesting that deriving oligosaccharide conformations basedon the conformational preferences of the constituent disaccharidefragments will not always yield correct results. Unlike otheroligomannoses, Man9GlcNAc2 appears to take more than one distinctconformation around the core 1,6-linkage. These various conformationsmay play an important role in determining the processing pathways.Using the data on the preferred conformations of these oligomannosesand the available experimental results, possible pathways forprocessing Man9GlcNAc2 to Man5GlcNAc2 by 1,2-linkage-specificmannosidases have been proposed. Conformational analysis ofMan5GlcNAc2 indicates that the addition of ß1,2-GlcNActo the 1,3-linked core mannose, besides serving as a prerequisitefor mannosidase II action as suggested earlier, may also preventthe removal of 1,3-mannose. The MD simulations also suggestthat the processing of the precursor oligosaccharide duringAsn-linked complex and hybrid glycan biosynthesis proceeds ina well-defined pathway involving more than one 1,2-linkage-specificmannosidase. Knowledge of the conformation of the processingintermediates obtained from the present study can be used todesign highly specific substrate analogues to inhibit a particularmannosidase, thereby blocking one processing pathway withoutinterfering with the others. carbohydrates conformation glycosidase inhibitors mannosidase oligosaccharide processing 相似文献
4.
The effect of Sargassum polycystum crude extract on lipid metabolism was examined against acetaminophen-induced (800 mg/kg body wt., intraperitoneally) hyperlipidemia during toxic hepatitis in experimental rats. The animals intoxicated with acetaminophen showed significant elevation in the levels of cholesterol, triglycerides and free fatty acid in both serum and liver tissue. The levels of tissue total lipids and serum LDL-cholesterol were also elevated with depleted levels of serum HDL-cholesterol and tissue phospholipid. The acetaminophen-induced animals showed significant alterations in the activities of lipid metabolizing enzymes serum lecithin cholesterol acyl transferase (LCAT) and hepatic triglyceride lipase (HTGL). The levels of liver tissue fatty acids (saturated, mono and polyunsaturated) such as palmitic acid, stearic acid, oleic acid, linoleic acid, arachidonic acid and linolenic acid monitored by gas chromatography were considerably altered in acetaminophen intoxicated animals when compared with control animals. The prior oral administration of Sargassum polycystum (200 mg/kg body wt./day for a period of 15 days) crude extract showed considerable prevention in the severe disturbances of lipid profile and metabolizing enzymes triggered by acetaminophen during hepatic injury. Liver histology also showed convincing supportive evidence regarding their protective nature against fatty changes induced during acetaminophen intoxication. Thus the present study indicates that the protective nature of Sargassum polycystum extract may be due to the presence of active compounds possessing antilipemic property against acetaminophen challenge. (Mol Cell Biochem 276: 89–96, 2005) 相似文献
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The CYP1A1 gene encodes for the enzyme, aryl hydrocarbon hydroxylase, which is involved in the biotransformation of various aromatic tobacco precarcinogens. In the present study, the association between CYP1A1 gene polymorphisms (IVS1-728G > A, Thr461Asn and Ile462Val), and the risk of oral cancer, was examined among 157 patients with oral cancer and 132 age-matched controls, in a south Indian population. The strength of the association between CYP1A1 variants and oral cancer was estimated by logistic regression. It was found that Thr461Asn was not polymorphic. Both IVS1-728G > A and Ile462Val frequencies were consistent with Hardy-Weinberg equilibrium in the control group. There were no significant differences in genotype or haplotype frequencies between controls and cases with oral cancer. Hence, CYP1A1 SNPs can be considered as not being associated with oral cancer at either the genotype or haplotype levels in the population studied. 相似文献
8.
In this study, we characterized a putative peroxidase Prx1 of Candida albicans by: 1) demonstrating the thioredoxin-linked peroxidase activity with purified proteins, 2) examining the sensitivity to several
oxidants and the accumulation of intracellular reactive oxygen species with a null mutant (prx1Δ), a mutant (C69S) with a point mutation at Cys69, and a revertant, and 3) subcelluar localization. Enzymatic assays showed
that Prx1 is a thioredoxin-linked peroxidase which reduces both hydrogen peroxide (H2O2) and tert-butyl hydroperoxide (t-BOOH). Compared with two other strong H2O2 scavenger mutants for TSA1 and CAT1, prx1Δ and C69S were less sensitive to H2O2, menadione and diamide at all concentrations tested, but were more sensitive to low concentration of t-BOOH. Intracellular reactive oxygen species accumulated in prx1Δ and C69S cells treated with t-BOOH but not H2O2. These results suggest that peroxidase activity of Prx1 is specified to t-BOOH in cells. In both biochemical and physiological cases, the evolutionarily conserved Cys69 was found to be essential
for the function. Immunocytochemical staining revealed Prx1 is localized in the cytosol of yeast cells, but is translocated
to the nucleus during the hyphal transition, though the significances of this observation are unclear. Our data suggest that
PRX1 has a thioredoxin peroxidase activity reducing both t-BOOH and H2O2, but its cellular function is specified to t-BOOH. 相似文献
9.
Kumudini Tota Nihar Rayabarapu Sowmya Moosa Venu Talla Balaji Bhyravbhatla Srinivasa Rao 《Bioinformation》2013,9(7):378-380
According to International Diabetes Federation (IDF), India has 62.4 million people with diabetes and by 2030 it is predicted that
the number will rise to 100 million. Studies claim that there are around 410 experimentally proven Indian medicinal plants which
have anti-diabetic activity, of which the mechanism of action of 109 plants has been elucidated or reported. So, the need of the hour
is to explore the claims of Indian medicinal flora and open up the facets of many Indian plants which are being examined for their
beneficial role in diabetes. So, we created a database (InDiaMed) of Indian medicinal plants that captures their role in anti-diabetic
activity. InDiaMed''s features include chemical, pharmacological, biochemical and geographical information of the medicinal plant,
scientifically relevant information of the plant, and the coherent research done on it in the field of diabetes. The database also
includes the list of poly-herbal formulations which are used for treatment of diabetes in India.
Availability
http://www.indiamed.info 相似文献10.