全文获取类型
收费全文 | 1510篇 |
免费 | 97篇 |
国内免费 | 2篇 |
出版年
2022年 | 11篇 |
2021年 | 20篇 |
2020年 | 12篇 |
2019年 | 8篇 |
2018年 | 20篇 |
2017年 | 17篇 |
2016年 | 40篇 |
2015年 | 56篇 |
2014年 | 69篇 |
2013年 | 88篇 |
2012年 | 122篇 |
2011年 | 115篇 |
2010年 | 71篇 |
2009年 | 55篇 |
2008年 | 91篇 |
2007年 | 88篇 |
2006年 | 98篇 |
2005年 | 88篇 |
2004年 | 101篇 |
2003年 | 73篇 |
2002年 | 59篇 |
2001年 | 6篇 |
2000年 | 11篇 |
1999年 | 21篇 |
1998年 | 17篇 |
1997年 | 12篇 |
1996年 | 9篇 |
1995年 | 11篇 |
1994年 | 18篇 |
1993年 | 12篇 |
1991年 | 8篇 |
1990年 | 6篇 |
1989年 | 9篇 |
1988年 | 4篇 |
1987年 | 4篇 |
1986年 | 6篇 |
1985年 | 6篇 |
1984年 | 7篇 |
1982年 | 8篇 |
1981年 | 9篇 |
1980年 | 9篇 |
1979年 | 5篇 |
1978年 | 4篇 |
1977年 | 6篇 |
1975年 | 4篇 |
1974年 | 5篇 |
1971年 | 5篇 |
1962年 | 5篇 |
1935年 | 4篇 |
1912年 | 4篇 |
排序方式: 共有1609条查询结果,搜索用时 312 毫秒
141.
Ghannam G Takeda A Camarata T Moore MA Viale A Yaseen NR 《The Journal of biological chemistry》2004,279(2):866-875
142.
143.
State of the art molecular dynamics simulations are used to study the structure, dynamics, molecular interaction properties and flexibility of DNA and RNA duplexes in aqueous solution. Special attention is paid to the deformability of both types of structures, revisiting concepts on the relative flexibility of DNA and RNA duplexes. Our simulations strongly suggest that the concepts of flexibility, rigidity and deformability are much more complex than usually believed, and that it is not always true that DNA is more flexible than RNA. 相似文献
144.
Induction of secretory phospholipase A2 in reactive astrocytes in response to transient focal cerebral ischemia in the rat brain 总被引:1,自引:0,他引:1
Lin TN Wang Q Simonyi A Chen JJ Cheung WM He YY Xu J Sun AY Hsu CY Sun GY 《Journal of neurochemistry》2004,90(3):637-645
Although mRNA expression of group IIA secretory phospholipase A2 (sPLA2-IIA) has been implicated in responses to injury in the CNS, information on protein expression remains unclear. In this study, we investigated temporal and spatial expression of sPLA2-IIA mRNA and immunoreactivity in transient focal cerebral ischemia induced in rats by occlusion of the middle cerebral artery. Northern blot analysis showed a biphasic increase in sPLA2-IIA mRNA expression following 60-min of ischemia-reperfusion: an early phase at 30 min and a second increase at a late phase ranging from 12 h to 14 days. In situ hybridization localized the early-phase increase in sPLA2-IIA mRNA to the affected ischemic cortex and the late-phase increase to the penumbral area. Besides sPLA2-IIA mRNA, glial fibrillary acidic protein (GFAP) and cyclo-oxygenase-2 mRNAs, but not cytosolic PLA2, also showed an increase in the penumbral area at 3 days after ischemia-reperfusion. Immunohistochemistry of sPLA2-IIA indicated positive cells in the penumbral area similar to the GFAP-positive astrocytes but different from the isolectin B4-positive microglial cells. Confocal microscopy further confirmed immunoreactivity of sPLA2-IIA in reactive astrocytes but not in microglial cells. Taken together, these results demonstrate for the first time an up-regulation of the inflammatory sPLA2-IIA in reactive astrocytes in response to cerebral ischemia-reperfusion. 相似文献
145.
Circulation of type 1 vaccine-derived poliovirus in the Philippines in 2001 总被引:14,自引:0,他引:14
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Shimizu H Thorley B Paladin FJ Brussen KA Stambos V Yuen L Utama A Tano Y Arita M Yoshida H Yoneyama T Benegas A Roesel S Pallansch M Kew O Miyamura T 《Journal of virology》2004,78(24):13512-13521
In 2001, highly evolved type 1 circulating vaccine-derived poliovirus (cVDPV) was isolated from three acute flaccid paralysis patients and one contact from three separate communities in the Philippines. Complete genomic sequencing of these four cVDPV isolates revealed that the capsid region was derived from the Sabin 1 vaccine strain but most of the noncapsid region was derived from an unidentified enterovirus unrelated to the oral poliovirus vaccine (OPV) strains. The sequences of the cVDPV isolates were closely related to each other, and the isolates had a common recombination site. Most of the genetic and biological properties of the cVDPV isolates were indistinguishable from those of wild polioviruses. However, the most recently identified cVDPV isolate from a healthy contact retained the temperature sensitivity and partial attenuation phenotypes. The sequence relationships among the isolates and Sabin 1 suggested that cVDPV originated from an OPV dose given in 1998 to 1999 and that cVDPV circulated along a narrow chain of transmission. Type 1 cVDPV was last detected in the Philippines in September 2001, and population immunity to polio was raised by extensive OPV campaigns in late 2001 and early 2002. 相似文献
146.
Gyetvai A Emri T Takács K Dergez T Fekete A Pesti M Pócsi I Lenkey B 《FEMS yeast research》2006,6(8):1140-1148
Lovastatin inhibited the growth of Candida albicans in a fungistatic way. Although it triggers apoptosis in a great variety of eukaryotic cells, including many tumour cell lines, lovastatin failed to provoke apoptotic events in this human pathogen. The fungistatic behaviour of this statin might arise from its negative influence on membrane fluidity. Because yeast-->pseudomycelium and hyphae morphogenetic transitions took place under exposure to lovastatin morphogenetic switch and apoptotic cell death must be regulated independently in C. albicans. 相似文献
147.
Agnes E Coutinho Jonathan E Campbell Sergiu Fediuc Michael C Riddell 《Journal of applied physiology》2006,100(5):1483-1488
Recent findings indicate that elevated levels of glucocorticoids (GC), governed by the expression of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) and GC receptors (GR), in visceral adipose tissue and skeletal muscle lead to increased insulin resistance and the metabolic syndrome. Paradoxically, evidence indicates that aerobic exercise attenuates the development of the metabolic syndrome even though it stimulates acute increases in circulating GC levels. To investigate the hypothesis that training alters peripheral GC action to maintain insulin sensitivity, young male hamsters were randomly divided into sedentary (S) and trained (T) groups (n = 8 in each). The T group had 24-h access to running wheels over 4 wk of study. In muscle, T hamsters had lower 11beta-HSD1 protein expression (19.2 +/- 1.40 vs. 22.2 +/- 0.96 optical density, P < 0.05), similar 11beta-HSD1 enzyme activity (0.9 +/- 0.27% vs. 1.1 +/- 0.26), and lower GR protein expression (9.7 +/- 1.86 vs. 15.1 +/- 1.78 optical density, P < 0.01) than S hamsters. In liver, 11beta-HSD1 protein expression tended to be lower in T compared with S (19.2 +/- 0.56 vs. 21.4 +/- 1.05, P = 0.07), whereas both enzyme activity and GR protein expression were similar. In contrast, visceral adipose tissue contained approximately 2.7-fold higher 11beta-HSD1 enzyme activity in T compared with S (12.9 +/- 3.3 vs. 4.8 +/- 1.5% conversion, P < 0.05) but was considerably smaller in mass (0.24 +/- 0.02 vs. 0.71 +/- 0.06 g). Thus the intracellular adaptation of GC regulators to exercise is tissue specific, resulting in decreases in GC action in skeletal muscle and increases in GC action in visceral fat. These adaptations may have important implications in explaining the protective effects of aerobic exercise on insulin resistance and other symptoms of the metabolic syndrome. 相似文献
148.
While numerous proteomic analyses have been carried out on Escherichia coli, the vast majority have focused on expression of intracellular proteins. Yet, recent literature reports imply that even in laboratory strains, significant proteins may be found outside the cell. Here, we identify extracellular proteins associated with nonpathogenic E. coli strain W3110. Two-dimensional gel electrophoresis (2DE) revealed approximately 66 prominent protein spots during exponential growth (4 and 8 h shake flask culture) in minimal medium. The absence of detectable nucleic acids in the culture supernatant implies these proteins did not result from cell lysis. MALDI-TOF MS was used to identify 44 proteins, most of which have been previously identified as either outer membrane or extracellular proteins. In addition, 2DE protease zymogram analysis was carried out which facilitated identification of three extracellular proteases, one of which was not observed during standard 2DE. Our results are consistent with previous findings which imply outer membrane proteins are shed during growth. 相似文献
149.
Zoltan Vajo John Wood Lajos Kosa Istvan Szilvasy Gyorgy Paragh Zsuzsanna Pauliny Kálmán Bartha Ildiko Visontay Agnes Kis Istvan Jankovics 《Journal of virology》2010,84(3):1237-1242
With the ongoing pandemic of influenza A (H1N1) virus infection and the threat of high fatality rates for recent human cases of infection with highly pathogenic H5N1 strains, there has been considerable interest in developing pandemic vaccines. Here we report a randomized multicenter dose-finding clinical trial of a whole-virion, inactivated, adjuvanted H5N1 vaccine in adult and elderly volunteers. Four hundred eighty patients were randomly assigned to receive one or two doses of 3.5 μg of the vaccine or one dose of 6 or 12 μg. The subjects were monitored for safety analysis, and serum samples were obtained to assess immunogenicity by hemagglutination inhibition and microneutralization tests. The subjects developed antibody responses against the influenza A (H5N1) virus. Single doses of ≥6 μg fulfilled EU and U.S. licensing criteria for interpandemic and pandemic influenza vaccines. Except for occasional injection site pain, malaise, and fever, no adverse events were observed. We found that the present vaccine is safe and immunogenic in healthy adult and elderly subjects and requires low doses and, unlike any other H5N1 vaccines, only one injection to trigger immune responses which comply with licensing criteria. A vaccine using the same methods as those described in this report, but based on a wild-type swine-origin 2009 (H1N1) influenza A virus isolate from the United States (supplied by the CDC), has been developed and is currently being tested by our group.With the ongoing pandemic of influenza A (H1N1) virus infection and the threat of high fatality rates for recent human cases of infection with highly pathogenic H5N1 strains, there has been considerable interest in developing pandemic influenza vaccines.With new cases continuing to emerge, as of June 2009, the avian influenza A (H5N1) virus subtype has caused 433 human infections in 15 countries, as confirmed by the World Health Organization (WHO), resulting in severe illness with a high fatality rate (30). Human-to-human spread has been strongly suspected and even evidenced by statistical methods (22, 33). With new human infections continuing to develop, this subtype continues to represent a potential source of an influenza pandemic (33).Mass vaccination is the most effective approach to reduce illness and death from pandemic influenza. Therefore, vaccine producers are currently developing and assessing vaccines against H5N1 viruses (2, 14, 31). The effects of split, subvirion, and whole-virion H5N1 vaccines have been tested, with various immunogenicity results (31). Three whole-virion vaccines have been tested so far, two of which required two-dose regimens (4, 14), while a one-dose regimen with the present vaccine was found to be immunogenic in 146 adult subjects (24).The objective of the present study was to determine the safety and immunogenicity of an inactivated whole-virion vaccine against influenza A/Vietnam/1194/2004, using multiple dosing and administration schedules, for adult and elderly subjects. To date, this is the only influenza pandemic prototype vaccine trial examining single-dose regimens in elderly patients. 相似文献
150.