全文获取类型
收费全文 | 4887篇 |
免费 | 387篇 |
国内免费 | 7篇 |
出版年
2023年 | 14篇 |
2022年 | 32篇 |
2021年 | 81篇 |
2020年 | 51篇 |
2019年 | 68篇 |
2018年 | 77篇 |
2017年 | 86篇 |
2016年 | 145篇 |
2015年 | 224篇 |
2014年 | 262篇 |
2013年 | 305篇 |
2012年 | 360篇 |
2011年 | 351篇 |
2010年 | 225篇 |
2009年 | 249篇 |
2008年 | 321篇 |
2007年 | 297篇 |
2006年 | 325篇 |
2005年 | 287篇 |
2004年 | 297篇 |
2003年 | 279篇 |
2002年 | 251篇 |
2001年 | 58篇 |
2000年 | 37篇 |
1999年 | 57篇 |
1998年 | 53篇 |
1997年 | 31篇 |
1996年 | 28篇 |
1995年 | 32篇 |
1994年 | 38篇 |
1993年 | 33篇 |
1992年 | 35篇 |
1991年 | 23篇 |
1990年 | 21篇 |
1989年 | 19篇 |
1988年 | 13篇 |
1987年 | 11篇 |
1986年 | 16篇 |
1985年 | 17篇 |
1984年 | 22篇 |
1983年 | 13篇 |
1982年 | 14篇 |
1981年 | 14篇 |
1980年 | 17篇 |
1979年 | 11篇 |
1978年 | 9篇 |
1977年 | 13篇 |
1976年 | 10篇 |
1975年 | 8篇 |
1974年 | 6篇 |
排序方式: 共有5281条查询结果,搜索用时 78 毫秒
951.
952.
953.
954.
Tobias Schwarzmüller Biao Ma Ekkehard Hiller Fabian Istel Michael Tscherner Sascha Brunke Lauren Ames Arnaud Firon Brian Green Vitor Cabral Marina Marcet-Houben Ilse D. Jacobsen Jessica Quintin Katja Seider Ingrid Frohner Walter Glaser Helmut Jungwirth Sophie Bachellier-Bassi Murielle Chauvel Ute Zeidler Dominique Ferrandon Toni Gabaldón Bernhard Hube Christophe d'Enfert Steffen Rupp Brendan Cormack Ken Haynes Karl Kuchler 《PLoS pathogens》2014,10(6)
The opportunistic fungal pathogen Candida glabrata is a frequent cause of candidiasis, causing infections ranging from superficial to life-threatening disseminated disease. The inherent tolerance of C. glabrata to azole drugs makes this pathogen a serious clinical threat. To identify novel genes implicated in antifungal drug tolerance, we have constructed a large-scale C. glabrata deletion library consisting of 619 unique, individually bar-coded mutant strains, each lacking one specific gene, all together representing almost 12% of the genome. Functional analysis of this library in a series of phenotypic and fitness assays identified numerous genes required for growth of C. glabrata under normal or specific stress conditions, as well as a number of novel genes involved in tolerance to clinically important antifungal drugs such as azoles and echinocandins. We identified 38 deletion strains displaying strongly increased susceptibility to caspofungin, 28 of which encoding proteins that have not previously been linked to echinocandin tolerance. Our results demonstrate the potential of the C. glabrata mutant collection as a valuable resource in functional genomics studies of this important fungal pathogen of humans, and to facilitate the identification of putative novel antifungal drug target and virulence genes. 相似文献
955.
956.
Michael A. Tabak Sally Poncet Ken Passfield Carlos Martinez del Rio 《Biological invasions》2014,16(2):341-352
Invasive species pose significant threats to biodiversity, especially on islands. They cause extinctions and population declines, yet little is known about their consequences on the emergent, metacommunity-level patterns of native species in island assemblages. We investigated differences in species–area relationships, nestedness, and occupancy of 9 species of native land birds between island assemblages with and without invasive Norway rats (Rattus norvegicus) in the Falkland Archipelago. We found that species–area curves, nestedness, and individual species’ occurrences differed between island assemblages with and without rats. Rat-free islands had, on average, 2.1 more land bird species than rat-infested islands of similar size. Passerine bird communities on islands with and without rats were significantly nested, but nestedness was significantly higher on rat-free islands than on rat-infested islands. The presence of rats was associated with differences in the incidence of many, but not all bird species. On rat free islands the occurrence of all species increased with island area. The occurrence of most, albeit not all, bird species was lower on islands with than on islands without rats. Two species of conservation concern, Troglodytes aedon cobbi and Cinclodes antarcticus, were abundant on rat-free islands, but absent or found at very low frequencies on islands with rats. The occurrence of three species was not associated with the presence of rats. The patterns presented here can be used to evaluate the consequences of ongoing rat eradications for passerine diversity, distribution, and abundance. 相似文献
957.
Determining the quality and complexity of next-generation sequencing data without a reference genome
Seyed Yahya Anvar Lusine Khachatryan Martijn Vermaat Michiel van Galen Irina Pulyakhina Yavuz Ariyurek Ken Kraaijeveld Johan T den Dunnen Peter de Knijff Peter AC ’t Hoen Jeroen FJ Laros 《Genome biology》2014,15(12)
We describe an open-source kPAL package that facilitates an alignment-free assessment of the quality and comparability of sequencing datasets by analyzing k-mer frequencies. We show that kPAL can detect technical artefacts such as high duplication rates, library chimeras, contamination and differences in library preparation protocols. kPAL also successfully captures the complexity and diversity of microbiomes and provides a powerful means to study changes in microbial communities. Together, these features make kPAL an attractive and broadly applicable tool to determine the quality and comparability of sequence libraries even in the absence of a reference sequence. kPAL is freely available at https://github.com/LUMC/kPAL.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0555-3) contains supplementary material, which is available to authorized users. 相似文献958.
Yanwen Jiang David Redmond Kui Nie Ken W Eng Thomas Clozel Peter Martin Leonard HC Tan Ari M Melnick Wayne Tam Olivier Elemento 《Genome biology》2014,15(8)
Background
Molecular mechanisms associated with frequent relapse of diffuse large B-cell lymphoma (DLBCL) are poorly defined. It is especially unclear how primary tumor clonal heterogeneity contributes to relapse. Here, we explore unique features of B-cell lymphomas - VDJ recombination and somatic hypermutation - to address this question.Results
We performed high-throughput sequencing of rearranged VDJ junctions in 14 pairs of matched diagnosis-relapse tumors, among which 7 pairs were further characterized by exome sequencing. We identify two distinctive modes of clonal evolution of DLBCL relapse: an early-divergent mode in which clonally related diagnosis and relapse tumors diverged early and developed in parallel; and a late-divergent mode in which relapse tumors developed directly from diagnosis tumors with minor divergence. By examining mutation patterns in the context of phylogenetic information provided by VDJ junctions, we identified mutations in epigenetic modifiers such as KMT2D as potential early driving events in lymphomagenesis and immune escape alterations as relapse-associated events.Conclusions
Altogether, our study for the first time provides important evidence that DLBCL relapse may result from multiple, distinct tumor evolutionary mechanisms, providing rationale for therapies for each mechanism. Moreover, this study highlights the urgent need to understand the driving roles of epigenetic modifier mutations in lymphomagenesis, and immune surveillance factor genetic lesions in relapse.Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0432-0) contains supplementary material, which is available to authorized users. 相似文献959.
Yukari Asai-Tajiri Koichiro Matsumoto Satoru Fukuyama Keiko Kan-o Takako Nakano Ken Tonai Tatsukuni Ohno Miyuki Azuma Hiromasa Inoue Yoichi Nakanishi 《Respiratory research》2014,15(1)
Background
CD86-CD28 interaction has been suggested as the principal costimulatory pathway for the activation and differentiation of naïve T cells in allergic inflammation. However, it remains uncertain whether this pathway also has an essential role in the effector phase. We sought to determine the contribution of CD86 on dendritic cells in the reactivation of allergen-specific Th2 cells.Methods
We investigated the effects of the downregulation of CD86 by short interfering RNAs (siRNAs) on Th2 cytokine production in the effector phase in vitro and on asthma phenotypes in ovalbumin (OVA)-sensitized and -challenged mice.Results
Treatment of bone marrow-derived dendritic cells (BMDCs) with CD86 siRNA attenuated LPS-induced upregulation of CD86. CD86 siRNA treatment impaired BMDCs’ ability to activate OVA-specific Th2 cells. Intratracheal administration of CD86 siRNA during OVA challenge downregulated CD86 expression in the airway mucosa. CD86 siRNA treatment ameliorated OVA-induced airway eosinophilia, airway hyperresponsiveness, and the elevations of OVA-specific IgE in the sera and IL-5, IL-13, and CCL17 in the bronchoalveolar lavage fluid, but not the goblet cell hyperplasia.Conclusion
These results suggest that local administration of CD86 siRNA during the effector phase ameliorates lines of asthma phenotypes. Targeting airway dendritic cells with siRNA suppresses airway inflammation and hyperresponsiveness in an experimental model of allergic asthma. 相似文献960.
Signatures of selection in sheep bred for resistance or susceptibility to gastrointestinal nematodes