全文获取类型
收费全文 | 545922篇 |
免费 | 60644篇 |
国内免费 | 345篇 |
专业分类
606911篇 |
出版年
2018年 | 5429篇 |
2017年 | 5232篇 |
2016年 | 7247篇 |
2015年 | 9272篇 |
2014年 | 10983篇 |
2013年 | 16009篇 |
2012年 | 17862篇 |
2011年 | 18201篇 |
2010年 | 12302篇 |
2009年 | 11222篇 |
2008年 | 15872篇 |
2007年 | 16489篇 |
2006年 | 15421篇 |
2005年 | 14825篇 |
2004年 | 14659篇 |
2003年 | 13948篇 |
2002年 | 13482篇 |
2001年 | 28517篇 |
2000年 | 28326篇 |
1999年 | 22130篇 |
1998年 | 6915篇 |
1997年 | 7445篇 |
1996年 | 6853篇 |
1995年 | 6336篇 |
1994年 | 6095篇 |
1993年 | 6065篇 |
1992年 | 17175篇 |
1991年 | 16386篇 |
1990年 | 15779篇 |
1989年 | 15306篇 |
1988年 | 14015篇 |
1987年 | 13021篇 |
1986年 | 12126篇 |
1985年 | 11906篇 |
1984年 | 9774篇 |
1983年 | 8189篇 |
1982年 | 6112篇 |
1981年 | 5482篇 |
1980年 | 5196篇 |
1979年 | 9005篇 |
1978年 | 6879篇 |
1977年 | 6334篇 |
1976年 | 5708篇 |
1975年 | 6285篇 |
1974年 | 6818篇 |
1973年 | 6583篇 |
1972年 | 6024篇 |
1971年 | 5474篇 |
1970年 | 4704篇 |
1969年 | 4429篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
51.
We have previously shown that replacing the P1-site residue (Ala) of chicken ovomucoid domain 3 (OMCHI3) with a Met or Lys results in the acquisition of inhibitory activity toward chymotrypsin or trypsin, respectively. However, the inhibitory activities thus induced are not strong. In the present study, we introduced additional amino acid replacements around the reactive site to try to make the P1-site mutants more effective inhibitors of chymotrypsin or trypsin. The amino acid replacement Asp-->Tyr at the P2' site of OMCHI3(P1Met) resulted in conversion to a 35000-fold more effective inhibitor of chymotrypsin with an inhibitor constant (K(i)) of 1. 17x10(-11) M. The K(i) value of OMCHI3(P1Met, P2'Ala) indicated that the effect on the interaction with chymotrypsin of removing a negative charge from the P2' site was greater than that of introducing an aromatic ring. Similarly, enhanced inhibition of trypsin was observed when the Asp-->Tyr replacement was introduced into the P2' site of OMCHI3(P1Lys). Two additional replacements, Asp-->Ala at the P4 site and Arg-->Ala at the P3' site, made the mutant a more effective inhibitor of trypsin with a K(i) value of 1. 44x10(-9) M. By contrast, Arg-->Ala replacement at the P3' site of OMCHI3(P1Met, P2'Tyr) resulted in a greatly reduced inhibition of chymotrypsin, and Asp-->Ala replacement at the P4 site produced only a small change when compared with a natural variant of OMCHI3. These results clearly indicate that not only the P1-site residue but also the characteristics, particularly the electrostatic properties, of the amino acid residues around the reactive site of the protease inhibitor determine the strength of its interactions with proteases. Furthermore, amino acids with different characteristics are required around the reactive site for strong inhibition of chymotrypsin and trypsin. 相似文献
52.
Z Zhong A Toukdarian D Helinski V Knauf S Sykes J E Wilkinson C O'Bryne T Shea C DeLoughery R Caspi 《Applied and environmental microbiology》2001,67(12):5771-5779
An agar-degrading marine bacterium identified as a Microscilla species was isolated from coastal California marine sediment. This organism harbored a single 101-kb circular DNA plasmid designated pSD15. The complete nucleotide sequence of pSD15 was obtained, and sequence analysis indicated a number of genes putatively encoding a variety of enzymes involved in polysaccharide utilization. The most striking feature was the occurrence of five putative agarase genes. Loss of the plasmid, which occurred at a surprisingly high frequency, was associated with loss of agarase activity, supporting the sequence analysis results. 相似文献
53.
Wendy A. Douglass Robert H. Hyland Christopher D. Buckley Aymen Al-Shamkhani Jacqueline M. Shaw Sarah L. Scarth David L. Simmons S.K.Alex Law 《FEBS letters》1998,440(3):125
The cysteine-rich region (CRR) of the β2 integrin subunit was replaced by that of β1 to give the chimera β2NV1. β2NV1 can combine with αL to form a variant leukocyte-function-associated antigen (LFA)-1 on COS cell surface, suggesting that the specificity of the β2 interaction with αL does not lie in the CRR. Unlike those expressing wild-type LFA-1, COS cells expressing αLβ2NV1 are constitutively active in intercellular adhesion molecule (ICAM)-1 adhesion. These results suggest that activation of LFA-1 involves the release of an intramolecular constraint, which is maintained, in part, by the authentic β2 CRR. 相似文献
54.
55.
D S Faffe G H Silva P M Kurtz E M Negri V L Capelozzi P R Rocco W A Zin 《Journal of applied physiology》2001,90(4):1400-1406
The dynamic mechanical properties of lung tissue and its contents of collagen and elastic fibers were studied in strips prepared from mice instilled intratracheally with saline (C) or silica [15 (S15) and 30 days (S30) after instillation]. Resistance, elastance, and hysteresivity were studied during oscillations at different frequencies on S15 and S30. Elastance increased from C to silica groups but was similar between S15 and S30. Resistance was augmented from C to S15 and S30 and was greater in S30 than in S15 at higher frequencies. Hysteresivity was higher in S30 than in C and S15. Silica groups presented a greater amount of collagen than did C. Elastic fiber content increased progressively along time. This increment was related to the higher amount of oxytalan fibers at 15 and 30 days, whereas elaunin and fully developed elastic fibers were augmented only at 30 days. Silicosis led not only to pulmonary fibrosis but also to fibroelastosis, thus assigning a major role to the elastic system in the silicotic lung. 相似文献
56.
S. I. Tkachenko A. R. Mingaleev V. M. Romanova A. E. Ter-Oganes’yan T. A. Shelkovenko S. A. Pikuz 《Plasma Physics Reports》2009,35(9):734-753
Distribution of matter in the discharge channel formed upon a nanosecond electrical explosion of a single wire in air and
vacuum was studied experimentally. Simultaneous use of optical, UV, and X-ray diagnostics made it possible to distinguish
qualitatively different regions of the discharge channel, such as the current-carrying layers and the region occupied by a
weakly conducting cold plasma. Several series of experiments with 25-μm-diameter 12-mm-long wires made of different materials
were performed. The charging voltage and the current amplitude were varied in the ranges of U
0 = 10–20 kV and I
max ∼ 5–10 kA, respectively. Explosion regimes with a current pause and with and without current interruption, as well as with
wire preheating in air and vacuum, were studied. Shadow and schlieren images of the discharge channel were obtained using
optical probing at the second harmonic of a YAG: Nd+3 laser (λ = 0.532 μm, τ ∼ 10 ns). In the experiments carried out in vacuum, X-ray images of the discharge channel were also
obtained using an X-pinch as a point source of probing radiation and UV images were recorded using a four-frame MCP camera. 相似文献
57.
Disseminated nocardiosis in three macaque monkeys 总被引:1,自引:0,他引:1
Extrapulmonary nocardiosis was diagnosed at necropsy in two rhesus monkeys (Macaca mulatta) and one pigtailed monkey (M. nemestrina) over a four-year period in a large primate center. Typical lesions were multiple pyogranulomatous foci in the liver, intestines, peritoneum, lung and brain. Partially acid-fast, branching, filamentous organisms were seen in all lesions. Nocardia sp. was isolated from two cases. We postulate that two of the monkeys were infected by the oral route because of the distribution of lesions. 相似文献
58.
Sensitization of mice with wild-type and cold-adapted influenza virus variants: immune response to two H1N1 and H3N2 viruses 下载免费PDF全文
Two A strain influenza viruses, A/Hong Kong/123/77 (A/HK/123/77) (H1N1) and A/Queensland/6/72 (A/Qld/6/72) (H3N2), and the two cold-adapted reassortants which possess the surface antigens of these strains (CR35 and CR6, respectively) were tested for their ability both to induce primary cytotoxic T-cell (Tc cell) responses in mice and to sensitize mice for a second Tc cell response when challenged with a distantly related A strain virus, A/Shearwater/72 (H6N5). After intranasal inoculation, A/Qld/6/72 replicated to higher titers in the lung (1 to 2 log10 50% egg infective doses) than did A/HK/123/77 or either of the reassortants. A/Qld/6/72 induced higher Tc cell responses in the lung than did CR6, and both were more effective than either A/HK/123/77 or CR35 in this respect. When similar doses (10 or 10(3) hemagglutinin units) of each virus were injected intravenously into mice and the spleens were tested for Tc cell activity 6 days later, both A/Qld/6/72 and CR6 were ca. 100-fold better at inducing a primary Tc cell response than A/HK/123/77 or CR35. In contrast, the H1N1 and H3N2 viruses gave rather similar anti-hemagglutinin antibody titers (after intravenous injection) and delayed-type hypersensitivity reactions (after subcutaneous injection). If mice were primed with a low dose of these viruses (10(4) 50% egg infective doses intranasally), A/Qld/6/72 and CR6 were more effective than A/HK/123/77 or CR35 at sensitizing for a secondary Tc cell response when challenged with A/Shearwater/72, but if larger doses were given either intranasally (10(6) 50% egg infective doses) or intravenously (10 to 10(3) hemagglutinin units), all viruses sensitized the mice equally well, despite the fact the A/Shearwater/72 gives a poor primary Tc cell response in mice. Thus, the viral glycoprotein antigens can be important in determining the immunogenicity of the virus and, particularly, the class I antigen-restricted Tc cell response of the host. 相似文献
59.
Anatomical and neurophysiological findings have demonstrated neuronal connections between the diencephalic habenular nuclei and brain stem serotonergic raphe nuclei. Therefore we examined some neurochemical consequences of habenular lesions. Sixteen hours and one week after bilateral lesions serotonin metabolism (as reflected by concentrations of its metabolite, 5-hydroxyindoleacetic acid) was significantly increased in the dorsal but not the median raphe nuclei. Unilateral lesions produced a proportionally smaller augmentation. Motron locomotor activity was enhanced during the light and dark illumination phases in lesioned animals but only attained statistical significance during the day. 相似文献
60.
M A Pass M W Goosem S Pollitt 《Comp. Biochem. Physiol. C, Comp. Pharmacol. Toxicol.》1985,82(2):457-461
The metabolism of the cholestatic triterpene acid reduced lantadene A has been studied in susceptible and resistant rats and in sheep which are susceptible to intoxication. Sheep and susceptible female rats produced a similar major metabolite and rats produced a second metabolite which was a glucuronide. These metabolites were also observed in extracts of bile canalicular membranes prepared from intoxicated rats. Resistant male and female rats produced a similar major metabolite which was different to those synthesized by susceptible animals. It is concluded that in rats and sheep there is a correlation between the type of metabolites produced in the liver and the susceptibility to intoxication by reduced lantadene A. 相似文献