全文获取类型
收费全文 | 20515篇 |
免费 | 1882篇 |
国内免费 | 229篇 |
出版年
2023年 | 98篇 |
2022年 | 194篇 |
2021年 | 455篇 |
2020年 | 283篇 |
2019年 | 319篇 |
2018年 | 406篇 |
2017年 | 353篇 |
2016年 | 535篇 |
2015年 | 898篇 |
2014年 | 916篇 |
2013年 | 1164篇 |
2012年 | 1380篇 |
2011年 | 1339篇 |
2010年 | 879篇 |
2009年 | 836篇 |
2008年 | 1133篇 |
2007年 | 1063篇 |
2006年 | 939篇 |
2005年 | 891篇 |
2004年 | 932篇 |
2003年 | 836篇 |
2002年 | 799篇 |
2001年 | 479篇 |
2000年 | 395篇 |
1999年 | 403篇 |
1998年 | 277篇 |
1997年 | 175篇 |
1996年 | 184篇 |
1995年 | 202篇 |
1994年 | 174篇 |
1993年 | 161篇 |
1992年 | 225篇 |
1991年 | 252篇 |
1990年 | 210篇 |
1989年 | 210篇 |
1988年 | 192篇 |
1987年 | 187篇 |
1986年 | 150篇 |
1985年 | 194篇 |
1984年 | 165篇 |
1983年 | 146篇 |
1982年 | 121篇 |
1981年 | 123篇 |
1980年 | 122篇 |
1979年 | 117篇 |
1978年 | 114篇 |
1977年 | 105篇 |
1976年 | 86篇 |
1974年 | 86篇 |
1973年 | 96篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
Protein Kinase PKR Mediates the Apoptosis Induction and Growth Restriction Phenotypes of C Protein-Deficient Measles Virus 总被引:1,自引:0,他引:1
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)
Ann M. Toth Patricia Devaux Roberto Cattaneo Charles E. Samuel 《Journal of virology》2009,83(2):961-968
The measles virus (MV) accessory proteins V and C play important roles in MV replication and pathogenesis. Infection with recombinant MV lacking either V or C causes more cell death than infection with the parental vaccine-equivalent virus (MVvac), and C-deficient virus grows poorly relative to the parental virus. Here, we show that a major effector of the C phenotype is the RNA-dependent protein kinase PKR. Using human HeLa cells stably deficient in PKR as a result of RNA interference-mediated knockdown (PKRkd cells), we demonstrated that a reduction in PKR partially rescued the growth defect of C knockout (Cko) virus but had no effect on the growth of either wild-type (WT) or V knockout (Vko) virus. Increased growth of the Cko virus in PKRkd cells correlated with increased viral protein expression, while defective growth and decreased protein expression in PKR-sufficient cells correlated with increased phosphorylation of PKR and the α subunit of eukaryotic initiation factor 2. Furthermore, infection with WT, Vko, or especially Cko virus caused significantly less apoptosis in PKRkd cells than in PKR-sufficient cells. Although apoptosis induced by Cko virus infection in PKR-sufficient cells was blocked by a caspase antagonist, the growth of Cko virus was not restored to the WT level by treatment with this pharmacologic inhibitor. Taken together, these results indicate that PKR plays an important antiviral role during MV infection but that the virus growth restriction by PKR is not dependent upon the induction of apoptosis. Furthermore, the results establish that a principal function of the MV C protein is to antagonize the proapoptotic and antiviral activities of PKR. 相似文献
2.
AAA ATPases form a functionally diverse superfamily of proteins. Most members form homo-hexameric ring complexes, are catalytically active only in the fully assembled state, and show co-operativity among the six subunits. The mutual dependence among the subunits is clearly evidenced by the fact that incorporation of mutated, inactive subunits can decrease the activity of the remaining wild type subunits. For the first time, we develop here models to describe this form of allostery, evaluate them in a simulation study, and test them on experimental data. We show that it is important to consider the assembly reactions in the kinetic model, and to define a formal inhibition scheme. We simulate three inhibition scenarios explicitly, and demonstrate that they result in differing outcomes. Finally, we deduce fitting formulas, and test them on real and simulated data. A non-competitive inhibition formula fitted experimental and simulated data best. To our knowledge, our study is the first one that derives and tests formal allosteric schemes to explain the inhibitory effects of mutant subunits on oligomeric enzymes. 相似文献
3.
Thirteen species of nematodes from the family Epsilonematidae Steiner, 1927 were found to be associated with a cold-water coral reef in the Porcupine Seabight. Among them, four species were already known from various locations such as Chile and Papua New Guinea. Three new species are described here: Glochinema trispinatumsp. n. is recognized by three dorsal thorns in the pharyngeal region. This species was also recovered from the Antarctic shelf. Epsilonema multispiralumsp. n. is characterised by a multispiral amphid consisting of 3.25 coils. Bathyepsilonema lopheliaesp. n. is characterised by its body length, the position and relative width of the amphids and the nature of the cuticular ornamentation. Within the subfamily Glochinematinae Lorenzen, 1974, the number and arrangement of ambulatory setae is considered not to be of diagnostic importance. The former species Metaglochinema strigosumGourbault & Decraemer, 1993 is therefore classified under the genus GlochinemaLorenzen, 1974. The original genus diagnosis of Metaglochinema, now a monotypic genus, is adjusted. The geographic distribution of epsilonematid nematodes is briefly discussed. 相似文献
4.
Nathalie Le Floc'h Céline Deblanc Roland Cariolet Anne V. Gautier-Bouchardon Elodie Merlot Ga?lle Simon 《PloS one》2014,9(8)
As nutritional status and inflammation are strongly connected, feeding and nutritional strategies could be effective to improve the ability of pigs to cope with disease. The aims of this study were to investigate the impact of a feed restriction on the ability of pigs to resist and be tolerant to a coinfection with Mycoplasma hyopneumoniae (Mhp) and the European H1N1 swine influenza virus, and the consequences for nutrient metabolism, with a focus on amino acids. Two groups of specific pathogen-free pigs were inoculated with Mhp and H1N1 21 days apart. One group was fed ad libitum, the other group was subjected to a two-week 40% feed restriction starting one week before H1N1 infection. The two respective mock control groups were included. Three days post-H1N1 infection, 200 g of feed was given to pigs previously fasted overnight and serial blood samples were taken over 4 hours to measure plasma nutrient concentrations. Throughout the study, clinical signs were observed and pathogens were detected in nasal swabs and lung tissues. Feed-restricted pigs presented shorter hyperthermia and a positive mean weight gain over the 3 days post-H1N1 infection whereas animals fed ad libitum lost weight. Both infection and feed restriction reduced postprandial glucose concentrations, indicating changes in glucose metabolism. Post-prandial plasma concentrations of the essential amino acids histidine, arginine and threonine were lower in co-infected pigs suggesting a greater use of those amino acids for metabolic purposes associated with the immune response. Altogether, these results indicate that modifying feeding practices could help to prepare animals to overcome an influenza infection. Connections with metabolism changes are discussed. 相似文献
5.
6.
Ann McElroy 《Medical anthropology quarterly》1998,12(4):512-515
Evolution of Sickness and Healing. Horacio Fábrega Jr. Berkeley: University of California Press, 1997 (cloth), xv. 364pp. 相似文献
7.
K Bejaoui S Le Bozec B Maton 《European journal of applied physiology and occupational physiology》1987,56(1):97-104
Reflex EMG responses to sudden passive flexion of the elbow were recorded from anconeus and triceps brachii in 5 human volunteers. While the subjects were required not to resist the flexion movement, they were required to maintain an extension torque of 3.5 or 7.0 Nm prior to its onset. Under these isotonic conditions, the latency and amplitude of the reflex activities from anconeus and triceps brachii did not differ significantly, in contrast to the findings of Le Bozec (1986) in actively relaxed subjects. The myotatic/postmyotatic EMG amplitude ratio did not provide a further quantitative way to distinguish between these muscles. The absence of a difference between the reflex activities of a slow (anconeus) and a fast (triceps brachii) muscle is interpreted as resulting from a strong drive of spindle activity on the whole extensor motoneuron pool, which outweights the differences in recruitment due to the differing relative amounts of type I and type II fibres in the two muscles. Differences like those described between finger and calf muscles by other authors are thought to be due to the relative degree of corticalization of these muscles. All short and long latency responses of the muscles increased in magnitude and decreased in latency with increasing background EMG activity as well as with increasing initial length. The position and tonic activity dependency of these responses is explained in terms of alpha-gamma coactivation. 相似文献
8.
9.
10.