全文获取类型
收费全文 | 9193篇 |
免费 | 562篇 |
国内免费 | 2篇 |
专业分类
9757篇 |
出版年
2023年 | 24篇 |
2022年 | 53篇 |
2021年 | 116篇 |
2020年 | 75篇 |
2019年 | 83篇 |
2018年 | 140篇 |
2017年 | 107篇 |
2016年 | 194篇 |
2015年 | 275篇 |
2014年 | 348篇 |
2013年 | 575篇 |
2012年 | 546篇 |
2011年 | 539篇 |
2010年 | 353篇 |
2009年 | 350篇 |
2008年 | 606篇 |
2007年 | 569篇 |
2006年 | 581篇 |
2005年 | 562篇 |
2004年 | 575篇 |
2003年 | 508篇 |
2002年 | 456篇 |
2001年 | 184篇 |
2000年 | 168篇 |
1999年 | 140篇 |
1998年 | 118篇 |
1997年 | 99篇 |
1996年 | 65篇 |
1995年 | 77篇 |
1994年 | 67篇 |
1993年 | 66篇 |
1992年 | 105篇 |
1991年 | 88篇 |
1990年 | 78篇 |
1989年 | 84篇 |
1988年 | 86篇 |
1987年 | 71篇 |
1986年 | 70篇 |
1985年 | 50篇 |
1984年 | 56篇 |
1983年 | 45篇 |
1982年 | 46篇 |
1981年 | 41篇 |
1980年 | 35篇 |
1979年 | 50篇 |
1978年 | 31篇 |
1977年 | 32篇 |
1976年 | 24篇 |
1974年 | 25篇 |
1973年 | 22篇 |
排序方式: 共有9757条查询结果,搜索用时 0 毫秒
991.
An enzyme "alkylaldoxime dehydratase (OxdRG)" was purified and characterized from Rhodococcus globerulus A-4, in which nitrile hydratase (NHase) and amidase coexisted with the enzyme. The enzyme contains heme b as a prosthetic group, requires reducing reagents for the reaction, and is most active at a neutral pH and at around 30 degrees C, similar to the phenylacetaldoxime dehydratase from Bacillus sp. OxB-1 (OxdB). However, some differences were seen in subunit structure, substrate specificity, and effects of activators and inhibitors. The corresponding gene, oxd, encoding a 1059-base pair ORF consisting of 353 codons, was cloned, sequenced, and overexpressed in Escherichia coli. The predicted polypeptide showed 30.3% identity to OxdB. The gene is mapped just upstream of the gene cluster encoding the enzymes involved in the metabolism of aliphatic nitriles, i.e., NHase and amidase, and their regulatory and activator proteins. We report here the existence of an aldoxime dehydratase genetically linked with NHase and amidase, and responsible for the metabolism of alkylaldoxime in R. globerulus. 相似文献
992.
Mizoribine monophosphate (MZP) is the active metabolite of the immunosuppressive agent mizoribine and a potent inhibitor of IMP dehydrogenase (IMPDH). This enzyme catalyzes the oxidation of IMP to XMP with the concomitant reduction of NAD via a covalent intermediate at Cys319 (E-XMP). Surprisingly, mutational analysis indicates that MZP is a transition state analogue although its structure does not resemble that of the expected transition state. Here we report the X-ray crystal structure of the E.MZP complex at 2.0 A resolution that reveals a transition state-like structure and solves the mechanistic puzzle of the IMPDH reaction. The protein assumes a new conformation where a flap folds into the NAD site and MZP, Cys319, and a water molecule are arranged in a geometry resembling the transition state. The water appears to be activated by interactions with a conserved Arg418-Tyr419 dyad. Mutagenesis experiments confirm that this new closed conformation is required for the hydrolysis of E-XMP, but not for the reduction of NAD. The closed conformation provides a structural explanation for the differences in drug selectivity and catalytic efficiency of IMPDH isozymes. 相似文献
993.
Firefly luciferase can catalyze the formation of fatty acyl-CoA via fatty acyl-adenylate from fatty acid in the presence of ATP, Mg2+ and coenzyme A (CoA). A long chain fatty acyl-CoA (C16–C20), produced by luciferase from a North American firefly (Photinus pyralis) and a Japanese firefly (Luciola cruciata), was isolated and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis. Of a number of substrates tested, linolenic acid (C18:3) and arachidonic acid (C20:4) appear to be suitable for acyl-CoA synthesis. This evidence suggests that firefly luciferase within peroxisomes of the cells in the photogenic organ may be a bifunctional enzyme, catalyzing not only the bioluminescence reaction but also the fatty acyl-CoA synthetic reaction. 相似文献
994.
Integration of cytochrome b(5) (b5), a tail-anchored protein located in the endoplasmic reticulum (ER) membrane, into the membrane was studied. Mutation of three amino acids, -Leu-Met-Tyr, at the carboxy-terminal end of the transmembrane segment of b5 to alanines resulted in localization of the mutated protein, b5LMY/AAA, in the cytosol as well as in the ER membrane. When an N-glycosylation site was introduced at the carboxy-terminal end of b5LMY/AAA, a substantial amount of the glycosylated form of the mutant protein was recovered in the cytosol fraction. A portion of the mutant protein recovered in the ER was released from the membrane by incubation with the cytosol fraction, but no further release was observed in the second incubation, suggesting that b5 is present in two different states, loosely-bound and firmly-integrated forms, in the ER membrane. These results suggest that b5 is integrated into the ER membrane via the loosely bound state, in which the carboxy-terminal end of the molecule is inserted into the luminal side of the vesicle but is easily translocated back to the cytosol, and that the three amino acids are important for conversion of the loosely-bound state to the firmly-integrated state. 相似文献
995.
996.
Fujimoto Z Kaneko S Momma M Kobayashi H Mizuno H 《The Journal of biological chemistry》2003,278(22):20313-20318
alpha-Galactosidases catalyze the hydrolysis of alpha-1,6-linked galactosyl residues from galacto-oligosaccharides and polymeric galacto-(gluco)mannans. The crystal structure of rice alpha-galactosidase has been determined at 1.5A resolution using the multiple isomorphous replacement method. The structure consisted of a catalytic domain and a C-terminal domain and was essentially the same as that of alpha-N-acetylgalactosaminidase, which is the same member of glycosyl hydrolase family 27. The catalytic domain had a (beta/alpha)8-barrel structure, and the C-terminal domain was made up of eight beta-strands containing a Greek key motif. The structure was solved as a complex with d-galactose, providing a mode of substrate binding in detail. The d-galactose molecule was found bound in the active site pocket on the C-terminal side of the central beta-barrel of the catalytic domain. The d-galactose molecule consisted of a mixture of two anomers present in a ratio equal to their natural abundance. Structural comparisons of rice alpha-galactosidase with chicken alpha-N-acetylgalactosaminidase provided further understanding of the substrate recognition mechanism in these enzymes. 相似文献
997.
998.
999.
A systematic investigation identifies a significant number of probable pseudogenes in the Escherichia coli genome 总被引:2,自引:0,他引:2
Pseudogenes are open reading frames (ORFs) encoding dysfunctional proteins with high homology to known protein-coding genes. Although pseudogenes were reported to exist in the genomes of many eukaryotes and bacteria, no systematic search for pseudogenes in the Escherichia coli genome has been carried out. Genome comparisons of E. coli strains K-12 and O157 revealed that many protein-coding sequences have prematurely terminated orthologs encoding unstable proteins. To systematically screen for pseudogenes, we selected ORFs generated by premature termination of the orthologous protein-coding genes and subsequently excluded those possibly arising from sequence errors. Lastly we eliminated those with close homologs in this and other species, as these shortened ORFs may actually have functions. The process produced 95 and 101 pseudogene candidates in K-12 and O157, respectively. The assigned three-dimensional structures suggest that most of the encoded proteins cannot fold properly and thus are dysfunctional, indicating that they are probably pseudogenes. Therefore, the existence of a significant number of probable pseudogenes in E. coli is predicted, awaiting experimental verification. Most of them were found to be genes with paralogs or horizontally transferred genes or both. We suggest that pseudogenes constitute a small fraction of the genomes of free-living bacteria in general, reflecting the faster elimination than production of pseudogenes. 相似文献
1000.
Akatsu H Abe M Miwa T Tateyama H Maeda S Okada N Kojima K Okada H 《Microbiology and immunology》2002,46(12):863-874
The anaphylatoxin, complement 5a (C5a), plays a key role in mediating various inflammatory reactions following complement activation. Several investigators have reported that C5a receptor (C5aR) is expressed in non-myeloid cells under certain conditions or in different cell lines. In our study, the abundance of C5aR-positive myeloid cells in rats depended on the organs examined. C5aR was usually expressed at the site of exposure to pathogens, such as in salivary gland or lung, and was up-regulated in liver in the inflammatory state induced by lipopolysaccharide (LPS) administration. Furthermore, the increased expression of C5aR antigen was not accompanied by an increase in C5aR mRNA in Kupffer cells following LPS challenge. 相似文献