全文获取类型
收费全文 | 101069篇 |
免费 | 9561篇 |
国内免费 | 4966篇 |
出版年
2023年 | 941篇 |
2022年 | 2196篇 |
2021年 | 3829篇 |
2020年 | 2508篇 |
2019年 | 3063篇 |
2018年 | 3164篇 |
2017年 | 2305篇 |
2016年 | 3325篇 |
2015年 | 5162篇 |
2014年 | 5961篇 |
2013年 | 6798篇 |
2012年 | 7870篇 |
2011年 | 7500篇 |
2010年 | 4492篇 |
2009年 | 4031篇 |
2008年 | 4950篇 |
2007年 | 4534篇 |
2006年 | 4008篇 |
2005年 | 3494篇 |
2004年 | 3053篇 |
2003年 | 2715篇 |
2002年 | 2479篇 |
2001年 | 3689篇 |
2000年 | 3537篇 |
1999年 | 2881篇 |
1998年 | 1306篇 |
1997年 | 1282篇 |
1996年 | 1212篇 |
1995年 | 1117篇 |
1994年 | 995篇 |
1993年 | 793篇 |
1992年 | 1541篇 |
1991年 | 1254篇 |
1990年 | 1111篇 |
1989年 | 937篇 |
1988年 | 748篇 |
1987年 | 627篇 |
1986年 | 531篇 |
1985年 | 460篇 |
1984年 | 353篇 |
1983年 | 302篇 |
1982年 | 195篇 |
1981年 | 202篇 |
1980年 | 147篇 |
1979年 | 206篇 |
1978年 | 145篇 |
1977年 | 154篇 |
1976年 | 145篇 |
1975年 | 148篇 |
1974年 | 162篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
M Shadidy X Caubit R Olsen O M Seternes U Moens S Krauss 《Biochimica et biophysica acta》1999,1446(3):295-307
We have identified mouse and human FKBP60, a new member of the FKBP gene family. FKBP60 shares strongest homology with FKBP65 and SMAP. FKBP60 contains a hydrophobic signal peptide at the N-terminus, 4 peptidyl-prolyl cis/trans isomerase (PPIase) domains and an endoplasmic reticulum retention motif (HDEL) at the C-terminus. Immunodetection of HA-tagged FKBP60 in NIH-3T3 cells suggests that FKBP60 is segregated to the endoplasmic reticulum. Northern blot analysis shows that FKBP60 is predominantly expressed in heart, skeletal muscle, lung, liver and kidney. With N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide as a substrate, recombinant GST-FKBP60 is shown to accelerate effectively the isomerization of the peptidyl-prolyl bond. This isomerization activity is inhibited by FK506. mFKBP60 binds Ca2+ in vitro, presumably by its C-terminal EF-hand Ca2+ binding motif, and is phosphorylated in vivo. hFKBP60 has been mapped to 7p12 and/or 7p14 by fluorescence in situ hybridization (FISH). 相似文献
2.
Plant Molecular Biology - 相似文献
3.
E Estébanez-Perpi?á A Bayés J Vendrell M A Jongsma D P Bown J A Gatehouse R Huber W Bode F X Avilés D Reverter 《Journal of molecular biology》2001,313(3):629-638
The cotton bollworm Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae) is one of the most serious insect pests in Australia, India and China. The larva causes substantial economical losses to legume, fibre, cereal oilseed and vegetable crops. This pest has proven to be difficult to control by conventional means, mainly due to the development of pesticide resistance. We present here the 2.5 A crystal structure from the novel procarboxypeptidase (PCPAHa) found in the gut extracts from H. armigera larvae, the first one reported for an insect. This metalloprotease is synthesized as a zymogen of 46.6 kDa which, upon in vitro activation with Lys-C endoproteinase, yields a pro-segment of 91 residues and an active carboxypeptidase moiety of 318 residues. Both regions show a three-dimensional structure quite similar to the corresponding structures in mammalian digestive carboxypeptidases, the most relevant structural differences being located in the loops between conserved secondary structure elements, including the primary activation site. This activation site contains the motif (Ala)(5)Lys at the C terminus of the helix connecting the pro- and the carboxypeptidase domains. A remarkable feature of PCPAHa is the occurrence of the same (Ala)(6)Lys near the C terminus of the active enzyme. The presence of Ser255 in PCPAHa instead of Ile and Asp found in the pancreatic A and B forms, respectively, enlarges the S1' specificity pocket and influences the substrate preferences of the enzyme. The C-terminal tail of the leech carboxypeptidase inhibitor has been modelled into the PCPAHa active site to explore the substrate preferences and the enzymatic mechanism of this enzyme. 相似文献
4.
Wen-Yeh Hsieh Tang-Ching Kuan Kun-Shan Cheng Yan-Chiou Liao Mu-Yuan Chen Pei-Heng Lin Yuan-Chang Hsu Chen-Yi Huang Wei-Hua Hsu Sheng-Yao Yu Chih-Sheng Lin 《International journal of biological sciences》2012,8(8):1197-1205
Objective: Pleural effusion is common problem, but the rapid and reliable diagnosis for specific pathogenic effusions are lacking. This study aimed to identify the diagnosis based on clinical variables to differentiate pleural tuberculous exudates from other pleural effusions. We also investigated the role of renin-angiotensin system (RAS) and matrix metalloproteinase (MMPs) in the pathogenesis of pleural exudates.Experimental design: The major components in RAS and extracellular matrix metabolism, including angiotensin converting enzyme (ACE), ACE2, MMP-2 and MMP-9 activities, were measured and compared in the patients with transudative (n = 45) and exudative (n = 80) effusions. The exudative effusions were come from the patients with tuberculosis (n = 20), pneumonia (n = 32), and adenocarcinoma (n = 28).Results: Increased ACE and equivalent ACE2 activities, resulting in a significantly increased ACE/ACE2 ratio in exudates, were detected compared to these values in transudates. MMP-9 activity in exudates was significantly higher than that in transudates. The significant correlation between ACE and ACE2 activity that was found in transudates was not found in exudates. Advanced analyses showed significantly increased ACE and MMP-9 activities, and decreased ACE2 activity in tuberculous pleural effusions compared with those in pneumonia and adenocarcinoma effusions. The results indicate that increased ACE and MMP-9 activities found in the exudates were mainly contributed from a higher level of both enzyme activities in the tuberculous pleural effusions.Conclusion: Interplay between ACE and ACE2, essential functions in the RAS, and abnormal regulation of MMP-9 probably play a pivotal role in the development of exudative effusions. Moreover, the ACE/ACE2 ratio combined with MMP-9 activity in pleural fluid may be potential biomarkers for diagnosing tuberculous pleurisy. 相似文献
5.
6.
7.
8.
9.
10.
A Yersinia pseudotuberculosis protein which cross-reacts with HLA-B27 总被引:10,自引:0,他引:10
J H Chen D H Kono Z Yong M S Park M M Oldstone D T Yu 《Journal of immunology (Baltimore, Md. : 1950)》1987,139(9):3003-3011
The most-debated question in the investigation of the spondyloarthropathies has been whether there is molecular mimicry between host HLA-B27 antigens and the arthritis-causing pathogens. We have generated a monoclonal anti-HLA-B27 antibody in our laboratory and have used a radioimmunoassay to screen a panel of bacterial species. Two strains of Yersinia pseudotuberculosis were found to be highly reactive. The cross-reactive Yersinia component was identified by Western blot to be a 19,000 component. A preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis chromatography apparatus was constructed to isolate milligram quantities of this component. To verify that the component carried the HLA-B27-specific epitope, rabbits were hyperimmunized with the purified materials. Affinity-purified antibodies from one of the immunized rabbits indeed carried anti-HLA-B27 activity. Last, antibodies generated against synthetic peptides derived from the HLA-B27.1 amino acid sequence were tested against the Yersinia component. Positive reactivity was found with antibodies generated against a peptide spanning residues 69-83 of the HLA-B27.1 protein. Since this resides in the segment responsible for the allotypic specificity of the antigen, these experiments establish the presence of molecular mimicry to a high degree of confidence. 相似文献