全文获取类型
收费全文 | 487854篇 |
免费 | 47560篇 |
国内免费 | 192篇 |
出版年
2018年 | 5064篇 |
2017年 | 4783篇 |
2016年 | 6233篇 |
2015年 | 6918篇 |
2014年 | 8774篇 |
2013年 | 12352篇 |
2012年 | 14340篇 |
2011年 | 14949篇 |
2010年 | 10159篇 |
2009年 | 9317篇 |
2008年 | 13381篇 |
2007年 | 13881篇 |
2006年 | 13377篇 |
2005年 | 12680篇 |
2004年 | 12652篇 |
2003年 | 12269篇 |
2002年 | 12167篇 |
2001年 | 24784篇 |
2000年 | 24835篇 |
1999年 | 19111篇 |
1998年 | 5685篇 |
1997年 | 5862篇 |
1996年 | 5419篇 |
1995年 | 4938篇 |
1994年 | 4875篇 |
1993年 | 4887篇 |
1992年 | 15039篇 |
1991年 | 15113篇 |
1990年 | 14641篇 |
1989年 | 14429篇 |
1988年 | 13431篇 |
1987年 | 12567篇 |
1986年 | 11422篇 |
1985年 | 11458篇 |
1984年 | 9065篇 |
1983年 | 7737篇 |
1982年 | 5384篇 |
1981年 | 4715篇 |
1980年 | 4569篇 |
1979年 | 8303篇 |
1978年 | 6411篇 |
1977年 | 5839篇 |
1976年 | 5411篇 |
1975年 | 6313篇 |
1974年 | 6765篇 |
1973年 | 6638篇 |
1972年 | 5935篇 |
1971年 | 5540篇 |
1970年 | 4825篇 |
1969年 | 4687篇 |
排序方式: 共有10000条查询结果,搜索用时 281 毫秒
911.
912.
In vivo neutralization of TNF-alpha promotes humoral autoimmunity by preventing the induction of CTL. 总被引:3,自引:0,他引:3
C S Via A Shustov V Rus T Lang P Nguyen F D Finkelman 《Journal of immunology (Baltimore, Md. : 1950)》2001,167(12):6821-6826
Neutralization of TNF-alpha in humans with rheumatoid arthritis or Crohn's disease has been associated with the development of humoral autoimmunity. To determine the effect of TNF-alpha neutralization on cell-mediated and humoral-mediated responses, we administered anti-TNF-alpha mAb to mice undergoing acute graft-vs-host disease (GVHD) using the parent-into-F(1) model. In vivo neutralization of TNF-alpha blocked the lymphocytopenic features characteristic of acute GVHD and induced a lupus-like chronic GVHD phenotype (lymphoproliferation and autoantibody production). These effects resulted from complete inhibition of detectable antihost CTL activity and required the presence of anti-TNF-alpha mAb for the first 4 days after parental cell transfer, indicating that TNF-alpha plays a critical role in the induction of CTL. Moreover, an in vivo blockade of TNF-alpha preferentially inhibited the production of IFN-gamma and blocked IFN-gamma-dependent up-regulation of Fas; however, cytokines such as IL-10, IL-6, or IL-4 were not inhibited. These results suggest that a therapeutic TNF-alpha blockade may promote humoral autoimmunity by selectively inhibiting the induction of a CTL response that would normally suppress autoreactive B cells. 相似文献
913.
914.
Frank H. T. Rhodes 《Journal of the history of biology》1987,20(2):139-157
Conclusion The major tenets of the recent hypothesis of punctuated equilibrium are explicit in Darwin's writing. His notes from 1837–1838 contain references to stasis and rapid change. In the first edition of the Origin (1859), Darwin described the importance of isolation of local varieties in the process of speciation. His views on the tempo of speciation were influenced by Hugh Falconer and also, perhaps, by Edward Suess (1831–1914). It is paradoxical that, although both topics were recorded in his unpublished notes of 1837–1838, the second was not explicitly and fully discussed until the fourth edition of the Origin (1866). While no wholly satisfactory explanation of this paradox suggests itself, it seems probable that Falconer's work on the persistence of fossil species of elephant helped Darwin to see the wider significance of the tempo of evolution for his general theory. 相似文献
915.
Rachael V. Gallagher Lesley Hughes Michelle R. Leishman Peter D. Wilson 《Biological invasions》2010,12(12):4049-4063
Potential interactions between climate change and exotic plant invasions may affect areas of high conservation value, such
as land set aside for the protection of endangered species or ecological communities. We investigated this issue in eastern
Australia using species distribution models for five exotic vines under climate regimes for 2020 and 2050. We examined how
projected changes in the distribution of climatically suitable habitat may coincide with the remaining remnants of an endangered
ecological community—littoral rainforests—in this region. The number of known infestations of each weed in tropical, subtropical
and temperate areas was used to assess the likelihood of further expansion into areas projected to provide suitable habitat
under future conditions. Littoral rainforest reserves were consistently predicted to provide bioclimatically suitable habitat
for the five vines examined under both current and future climate scenarios. We explore the consequences and potential strategies
for managing exotic plant invasions in these protected areas in the coming decades. 相似文献
916.
We used a N-biotinylated peptide analog of the C-terminal domain of the tumor suppressor protein, p21cip1/waf1 to elucidate peptide/protein interacting partners. The C-terminal domain of p21cip1/waf1 protein spanning 141-160 amino acid residues is known to bind PCNA and this interaction is important in many biological processes including cell-cycle control. This C-terminal 20-mer efficiently extracts PCNA in the presence of a variety of N- or C-terminally attached affinity tags. Using difference silver stained 2D gels combined with in-gel tryptic digests, we identified the difference spots using MALDI-TOF mass spectrometry-based peptide mass fingerprinting followed by a database search using PROFOUND against NCBIs human nonredundant protein sequence data bank. Identified spots include the p48 subunit of chromatin assembly factor-1, the heat shock 70 protein analog BiP, calmodulin, nucleolin and a spot similar in size to dimeric PCNA. In contrast, microcapillary ion-trap LC-MS/MS analysis of a tryptic digest of entire affinity extracts derived from both control and experimental runs followed by database searches using SEQUEST confirmed the presence of most of the above proteins. This strategy also identified hnRNPA1, HPSP90alpha, HSP40 and T-complex protein 1, a protein similar to prothymosin, and a possible allelic variant of the p21cip1/waf1 protein. The use of N-biotinylated peptide derived from the C-terminal domain of p21cip1/waf1 protein in proteomic analysis exemplified here suggests that peptides obtained from intracellular functional screens could also potentially serve as efficient baits to discover new drug targets. 相似文献
917.
Timothy J. French Anthony W. Good T. Norman Palmer Mary C. Sugden 《Bioscience reports》1985,5(9):729-734
The in vivo effects of dexamethasone administration on liver and extrahepatic tissue carnitine concentrations were assessed in 48-h-starved rats. In heart and kidney, but not in liver, dexamethasone significantly increased total carnitine concentration. Acute (2.5 h) treatment with 2-tetradecylglycidate (TDG), a specific inhibitor of carnitine palmitoyl transferase 1, not only increased total hepatic carnitine concentrations, but also permitted an effect of dexamethasone (a further increase in hepatic carnitine concentration). The results are discussed in terms of acute (substrate-mediated) and chronic (hormonal) control of carnitine turnover. 相似文献
918.
We have cloned and sequenced the p53-encoding cDNA of Syrian hamster. The encoded product is 78% and 75% homologous to human and mouse p53, respectively. Immunoprecipitations of the cDNA-encoded protein by monoclonal antibodies specific for mammalian p53 confirmed the identity of the protein. 相似文献
919.
A L Lobashevski? V S Chernyshov D Ia Bakanova A V Marchenkova 《Zhurnal mikrobiologii, epidemiologii, i immunobiologii》1985,(11):46-50
The influence of Gram-negative bacteria on the migratory and adhesive activity of polymorphonuclear leukocytes (PMNL) in the peripheral blood of clinically normal donors has been studied by the specially developed method with the use of Boyden chambers. Pseudomonas and enterobacteria have been found to produce complex and various effects on the above-mentioned properties of PMNL. When incubated in fresh serum, Gram-negative bacteria are capable of enhancing the migratory activity of PMNL, this property being least pronounced in P. aeruginosa. The incubation of live bacteria from the authors' collection in the patients' sera or in sera obtained from normal donors and inactivated by heating induces no hemotaxis of PMNL, and P. aeruginosa strains even suppress it under such conditions. The isolated Gram-negative bacteria under study increase the number of highly adhesive PMNL in the population used in this investigation, but P. aeruginosa cultures do not produce such effect. 相似文献
920.
C Grenot A de Montard T Blachère M R de Ravel E Mappus C Y Cuilleron 《Biochemistry》1992,31(33):7609-7621
Immunopurified human sex hormone binding globulin (SHBG) was photoinactivated and photolabeled by radioinert and radioactive photoaffinity labeling steroids delta 6-testosterone (delta 6-T) and delta 6-estradiol (delta 6-E2). The maximal levels of specific incorporation of these two reagents were 0.50 and 0.33 mol of label/mol of SHBG, respectively. Covalently labeled SHBG fractions were citraconylated, reduced, carboxymethylated, and cleaved by trypsin. Separation of tryptic digests by reverse-phase liquid chromatography gave single radioactive peaks at the same retention times with both steroid reagents. However, the two labeled peptidic fractions could be distinguished by capillary electrophoresis and immunodetection with anti-steroid antibodies, whereas the covalent attachment of radioactivity was confirmed by thin-layer chromatography on silica gel. Edman degradation of the two labeled peptides showed a single sequence His-Pro-Ile-([3H]X)-Arg corresponding to the pentapeptide His-Pro-Ile-Met-Arg 136-140 of SHBG sequence. The coincidence, in both cases, of the absence of an identifiable amino acid residue and of the elution of the most intense peak of radioactivity at the fourth cycle of Edman degradation suggests that the same Met-139 residue was labeled by delta 6-[1,2-3H2]T or by delta 6-[17 alpha-3H]E2. Liquid secondary ion mass spectrometry of the two peptides showed [M+H]+ ions at m/z 939.8 or 923.8, corresponding respectively to the addition of delta 6-T or delta 6-E2 to the pentapeptide. The presence of the steroid molecule in the delta 6-[3H]T-pentapeptide conjugate was confirmed by the difference of 2 mass units with the [M+H]+ peak of the delta 6-[4-14C]T-pentapeptide conjugate. 相似文献