全文获取类型
收费全文 | 2761篇 |
免费 | 203篇 |
国内免费 | 1篇 |
出版年
2023年 | 24篇 |
2022年 | 44篇 |
2021年 | 72篇 |
2020年 | 56篇 |
2019年 | 74篇 |
2018年 | 113篇 |
2017年 | 90篇 |
2016年 | 117篇 |
2015年 | 142篇 |
2014年 | 140篇 |
2013年 | 192篇 |
2012年 | 227篇 |
2011年 | 218篇 |
2010年 | 147篇 |
2009年 | 102篇 |
2008年 | 153篇 |
2007年 | 156篇 |
2006年 | 157篇 |
2005年 | 116篇 |
2004年 | 97篇 |
2003年 | 99篇 |
2002年 | 80篇 |
2001年 | 46篇 |
2000年 | 19篇 |
1999年 | 18篇 |
1998年 | 17篇 |
1997年 | 9篇 |
1996年 | 13篇 |
1995年 | 13篇 |
1994年 | 18篇 |
1993年 | 11篇 |
1992年 | 7篇 |
1991年 | 12篇 |
1990年 | 9篇 |
1989年 | 10篇 |
1988年 | 14篇 |
1986年 | 7篇 |
1984年 | 7篇 |
1983年 | 8篇 |
1982年 | 6篇 |
1981年 | 7篇 |
1979年 | 8篇 |
1975年 | 8篇 |
1974年 | 7篇 |
1973年 | 5篇 |
1972年 | 6篇 |
1970年 | 6篇 |
1969年 | 6篇 |
1968年 | 6篇 |
1964年 | 5篇 |
排序方式: 共有2965条查询结果,搜索用时 734 毫秒
101.
102.
103.
104.
105.
Nachtigal P Pospisilova N Jamborova G Pospechova K Solichova D Andrys C Zdansky P Semecky V 《Canadian journal of physiology and pharmacology》2007,85(8):767-773
Endoglin (CD105) is a homodimeric transmembrane glycoprotein strongly related to transforming growth factor (TGF)-beta signaling and many pathological states. In this study, we wanted to evaluate whether endoglin is expressed in normocholesterolemic and hypercholesterolemic C57BL/6J mice as well as whether it is affected by atorvastatin treatment in these mice. C57BL/6J mice were fed with chow diet or an atherogenic diet for 12 weeks after weaning. In 2 atorvastatin-treated groups, mice were fed the same diets (chow or atherogenic) as described above except atorvastatin was added at the dosage of 10 mg x kg(-1) x day(-1) for the last 8 weeks before euthanasia. Biochemical analysis of blood samples revealed that administration of atherogenic diet significantly increased levels of total cholesterol, VLDL, LDL, and decreased levels of HDL. Atorvastatin treatment resulted in a significant decrease in total cholesterol and VLDL only in mice fed by atherogenic diet. Quantitative stereological analysis revealed that atorvastatin significantly decreased endothelial expression of endoglin in C57BL/6J mice fed the atherogenic diet. In conclusion, we demonstrated that endothelial expression of endoglin is upregulated by hypercholesterolemia and decreased by the hypolipidemic effect of atorvastatin in C57BL/6J mice, suggesting that endoglin expression could be involved in atherogenesis. 相似文献
106.
107.
Weitz D Harder D Casagrande F Fotiadis D Obrdlik P Kelety B Daniel H 《The Journal of biological chemistry》2007,282(5):2832-2839
The ydgR gene of Escherichia coli encodes a protein of the proton-dependent oligopeptide transporter (POT) family. We cloned YdgR and overexpressed the His-tagged fusion protein in E. coli BL21 cells. Bacterial growth inhibition in the presence of the toxic phosphonopeptide alafosfalin established YgdR functionality. Transport was abolished in the presence of the proton ionophore carbonyl cyanide p-chlorophenylhydrazone, suggesting a proton-coupled transport mechanism. YdgR transports selectively only di- and tripeptides and structurally related peptidomimetics (such as aminocephalosporins) with a substrate recognition pattern almost identical to the mammalian peptide transporter PEPT1. The YdgR protein was purified to homogeneity from E. coli membranes. Blue native-polyacrylamide gel electrophoresis and transmission electron microscopy of detergent-solubilized YdgR suggest that it exists in monomeric form. Transmission electron microscopy revealed a crown-like structure with a diameter of approximately 8 nm and a central density. These are the first structural data obtained from a proton-dependent peptide transporter, and the YgdR protein seems an excellent model for studies on substrate and inhibitor interactions as well as on the molecular architecture of cell membrane peptide transporters. 相似文献
108.
A reverse genetics approach was utilized to discover new proteins that interact with the mitochondrial fusion mediator mitofusin 2 (Mfn2) and that may participate in mitochondrial fusion. In particular, in vivo formaldehyde cross-linking of whole HeLa cells and immunoprecipitation with purified Mfn2 antibodies of SDS cell lysates were used to detect an approximately 42-kDa protein. This protein was identified by liquid chromatography and tandem mass spectrometry as stomatin-like protein 2 (Stoml2), previously described as a peripheral plasma membrane protein of unknown function associated with the cytoskeleton of erythrocytes (Wang, Y., and Morrow, J. S. (2000) J. Biol. Chem. 275, 8062-8071). Immunoblot analysis with anti-Stoml2 antibodies showed that Stoml2 could be immunoprecipitated specifically with Mfn2 antibody either from formaldehyde-cross-linked and SDS-lysed cells or from cells lysed with digitonin. Subsequent immunocytochemistry and cell fractionation experiments fully supported the conclusion that Stoml2 is indeed a mitochondrial protein. Furthermore, demonstration of mitochondrial membrane potential-dependent import of Stoml2 accompanied by proteolytic processing, together with the results of sublocalization experiments, suggested that Stoml2 is associated with the inner mitochondrial membrane and faces the intermembrane space. Notably, formaldehyde cross-linking revealed a "ladder" of high molecular weight protein species, indicating the presence of high molecular weight Stoml2-Mfn2 hetero-oligomers. Knockdown of Stoml2 by the short interfering RNA approach showed a reduction of the mitochondrial membrane potential, without, however, any obvious changes in mitochondrial morphology. 相似文献
109.
NADH dehydrogenase activity was characterized in the mitochondrial lysates of Phytomonas serpens, a trypanosomatid flagellate parasitizing plants. Two different high molecular weight NADH dehydrogenases were characterized by native PAGE and detected by direct in-gel activity staining. The association of NADH dehydrogenase activities with two distinct multisubunit complexes was revealed in the second dimension performed under denaturing conditions. One subunit present in both complexes cross-reacted with the antibody against the 39 kDa subunit of bovine complex I. Out of several subunits analyzed by MS, one contained a domain characteristic for the LYR family subunit of the NADH:ubiquinone oxidoreductases. Spectrophotometric measurement of the NADH:ubiquinone 10 and NADH:ferricyanide dehydrogenase activities revealed their different sensitivities to rotenone, piericidin, and diphenyl iodonium. 相似文献
110.
Kujawa M Volc J Halada P Sedmera P Divne C Sygmund C Leitner C Peterbauer C Haltrich D 《The FEBS journal》2007,274(3):879-894
We purified an extracellular pyranose dehydrogenase (PDH) from the basidiomycete fungus Agaricus xanthoderma using ammonium sulfate fractionation and ion-exchange and hydrophobic interaction chromatography. The native enzyme is a monomeric glycoprotein (5% carbohydrate) containing a covalently bound FAD as its prosthetic group. The PDH polypeptide consists of 575 amino acids and has a molecular mass of 65 400 Da as determined by MALDI MS. On the basis of the primary structure of the mature protein, PDH is a member of the glucose-methanol-choline oxidoreductase family. We constructed a homology model of PDH using the 3D structure of glucose oxidase from Aspergillus niger as a template. This model suggests a novel type of bi-covalent flavinylation in PDH, 9-S-cysteinyl, 8-alpha-N3-histidyl FAD. The enzyme exhibits a broad sugar substrate tolerance, oxidizing structurally different aldopyranoses including monosaccharides and oligosaccharides as well as glycosides. Its preferred electron donor substrates are D-glucose, D-galactose, L-arabinose, and D-xylose. As shown by in situ NMR analysis, D-glucose and D-galactose are both oxidized at positions C2 and C3, yielding the corresponding didehydroaldoses (diketoaldoses) as the final reaction products. PDH shows no detectable activity with oxygen, and its reactivity towards electron acceptors is rather limited, reducing various substituted benzoquinones and complexed metal ions. The azino-bis-(3-ethylbenzthiazolin-6-sulfonic acid) cation radical and the ferricenium ion are the best electron acceptors, as judged by the catalytic efficiencies (k(cat)/K(m)). The enzyme may play a role in lignocellulose degradation. 相似文献