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941.
Alizon S von Wyl V Stadler T Kouyos RD Yerly S Hirschel B Böni J Shah C Klimkait T Furrer H Rauch A Vernazza PL Bernasconi E Battegay M Bürgisser P Telenti A Günthard HF Bonhoeffer S;Swiss HIV Cohort Study 《PLoS pathogens》2010,6(9):e1001123
HIV virulence, i.e. the time of progression to AIDS, varies greatly among patients. As for other rapidly evolving pathogens of humans, it is difficult to know if this variance is controlled by the genotype of the host or that of the virus because the transmission chain is usually unknown. We apply the phylogenetic comparative approach (PCA) to estimate the heritability of a trait from one infection to the next, which indicates the control of the virus genotype over this trait. The idea is to use viral RNA sequences obtained from patients infected by HIV-1 subtype B to build a phylogeny, which approximately reflects the transmission chain. Heritability is measured statistically as the propensity for patients close in the phylogeny to exhibit similar infection trait values. The approach reveals that up to half of the variance in set-point viral load, a trait associated with virulence, can be heritable. Our estimate is significant and robust to noise in the phylogeny. We also check for the consistency of our approach by showing that a trait related to drug resistance is almost entirely heritable. Finally, we show the importance of taking into account the transmission chain when estimating correlations between infection traits. The fact that HIV virulence is, at least partially, heritable from one infection to the next has clinical and epidemiological implications. The difference between earlier studies and ours comes from the quality of our dataset and from the power of the PCA, which can be applied to large datasets and accounts for within-host evolution. The PCA opens new perspectives for approaches linking clinical data and evolutionary biology because it can be extended to study other traits or other infectious diseases. 相似文献
942.
Jos H.M. Lange Martina A.W. van der Neut Arnold P. den Hartog Henri C. Wals Jan Hoogendoorn Herman H. van Stuivenberg Bernard J. van Vliet Chris G. Kruse 《Bioorganic & medicinal chemistry letters》2010,20(5):1752-1757
The synthesis, structure–activity relationship (SAR) studies and intramolecular hydrogen bonding pattern of 1,3,5-trisubstituted 4,5-dihydropyrazoles are described. The target compounds 6–18 represent a novel class of potent and selective CB1 receptor antagonists. Based on X-ray diffraction data, the orally active 17 is shown to elicit a different intramolecular H-bonding mode as compared to ibipinabant (3) and SLV330 (4). 相似文献
943.
944.
945.
Soline Vigneau Florence Levillayer Herv Crespeau Laurence Cattolico Bernard Caudron Franck Bihl Catherine Robert Michel Brahic Jean Weissenbach Jean-Franois Bureau 《Genomics》2001,78(3):206-213
We sequenced a 173-kb region of mouse chromosome 10, telomeric to the Ifng locus, and compared it with the human homologous sequence located on chromosome 12q15 using various sequence analysis programs. This region has a low density of genes: one gene was detected in the mouse and the human sequences and a second gene was detected only in the human sequence. The mouse gene and its human orthologue, which are expressed in the immune system at a low level, produce a noncoding mRNA. Nonexpressed sequences show a higher degree of conservation than exons in this genomic region. At least three of these conserved sequences are also conserved in a third mammalian species (sheep or cow). 相似文献
946.
947.
The liassic beds of the High-Atlas of Marrakech are rarely fossiliferous so all paleontological discoveries must be reported in order to give more biostratigraphical precisions for the interpretations of the sourcestrata basin. Palynological investigations in section composed of marl and dolomites with gypsum yield assemblages which the overall composition is characterized by the general dominance of Corollina in combination with relatively rare occurence of others nonsaccate pollen grains. Because the comparison of the associations previously described from the Lower Jurassic of Morocco and Sahara and the fact that the richness of Corollina has no stratigraphical value, the assemblages from the Telouat' section can be reasonably regarded to be indicative of a Sinemurian age. 相似文献
948.
Bernard Perbal 《Journal of cell communication and signaling》2008,2(3-4):57-57
We kindly invite you to consider the Journal of Cell Communication and Signaling (JCCS) as a media for publication of your research and participate in promoting JCCS as an important platform for disseminating new results in the fields of cell signaling. 相似文献
949.
Vince JE Wong WW Khan N Feltham R Chau D Ahmed AU Benetatos CA Chunduru SK Condon SM McKinlay M Brink R Leverkus M Tergaonkar V Schneider P Callus BA Koentgen F Vaux DL Silke J 《Cell》2007,131(4):682-693
XIAP prevents apoptosis by binding to and inhibiting caspases, and this inhibition can be relieved by IAP antagonists, such as Smac/DIABLO. IAP antagonist compounds (IACs) have therefore been designed to inhibit XIAP to kill tumor cells. Because XIAP inhibits postmitochondrial caspases, caspase 8 inhibitors should not block killing by IACs. Instead, we show that apoptosis caused by an IAC is blocked by the caspase 8 inhibitor crmA and that IAP antagonists activate NF-kappaB signaling via inhibtion of cIAP1. In sensitive tumor lines, IAP antagonist induced NF-kappaB-stimulated production of TNFalpha that killed cells in an autocrine fashion. Inhibition of NF-kappaB reduced TNFalpha production, and blocking NF-kappaB activation or TNFalpha allowed tumor cells to survive IAC-induced apoptosis. Cells treated with an IAC, or those in which cIAP1 was deleted, became sensitive to apoptosis induced by exogenous TNFalpha, suggesting novel uses of these compounds in treating cancer. 相似文献
950.
A key presynaptic role in transformation for a widespread bacterial protein: DprA conveys incoming ssDNA to RecA 总被引:3,自引:0,他引:3
Mortier-Barrière I Velten M Dupaigne P Mirouze N Piétrement O McGovern S Fichant G Martin B Noirot P Le Cam E Polard P Claverys JP 《Cell》2007,130(5):824-836
Natural transformation is a mechanism for genetic exchange in many bacterial genera. It proceeds through the uptake of exogenous DNA and subsequent homology-dependent integration into the genome. In Streptococcus pneumoniae, this integration requires the ubiquitous recombinase, RecA, and DprA, a protein of unknown function widely conserved in bacteria. To unravel the role of DprA, we have studied the properties of the purified S. pneumoniae protein and its Bacillus subtilis ortholog (Smf). We report that DprA and Smf bind cooperatively to single-stranded DNA (ssDNA) and that these proteins both self-interact and interact with RecA. We demonstrate that DprA-RecA-ssDNA filaments are produced and that these filaments catalyze the homology-dependent formation of joint molecules. Finally, we show that while the Escherichia coli ssDNA-binding protein SSB limits access of RecA to ssDNA, DprA lowers this barrier. We propose that DprA is a new member of the recombination-mediator protein family, dedicated to natural bacterial transformation. 相似文献