全文获取类型
收费全文 | 3847篇 |
免费 | 302篇 |
出版年
2024年 | 2篇 |
2023年 | 33篇 |
2022年 | 24篇 |
2021年 | 156篇 |
2020年 | 82篇 |
2019年 | 104篇 |
2018年 | 119篇 |
2017年 | 100篇 |
2016年 | 142篇 |
2015年 | 249篇 |
2014年 | 263篇 |
2013年 | 272篇 |
2012年 | 447篇 |
2011年 | 370篇 |
2010年 | 213篇 |
2009年 | 182篇 |
2008年 | 267篇 |
2007年 | 243篇 |
2006年 | 171篇 |
2005年 | 164篇 |
2004年 | 122篇 |
2003年 | 114篇 |
2002年 | 93篇 |
2001年 | 28篇 |
2000年 | 21篇 |
1999年 | 27篇 |
1998年 | 15篇 |
1997年 | 7篇 |
1996年 | 6篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1993年 | 9篇 |
1992年 | 10篇 |
1991年 | 11篇 |
1990年 | 6篇 |
1989年 | 8篇 |
1988年 | 5篇 |
1987年 | 5篇 |
1986年 | 7篇 |
1985年 | 3篇 |
1984年 | 4篇 |
1983年 | 6篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1979年 | 4篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1964年 | 2篇 |
1933年 | 2篇 |
1932年 | 1篇 |
排序方式: 共有4149条查询结果,搜索用时 15 毫秒
991.
Glas J Seiderer J Tillack C Pfennig S Beigel F Jürgens M Olszak T Laubender RP Weidinger M Müller-Myhsok B Göke B Ochsenkühn T Lohse P Diegelmann J Czamara D Brand S 《PloS one》2010,5(12):e14466
Background
The aims were to analyze two novel NOD2 variants (rs2066843 and rs2076756) in a large cohort of patients with inflammatory bowel disease and to elucidate phenotypic consequences.Methodology/Principal Findings
Genomic DNA from 2700 Caucasians including 812 patients with Crohn''s disease (CD), 442 patients with ulcerative colitis (UC), and 1446 healthy controls was analyzed for the NOD2 SNPs rs2066843 and rs2076756 and the three main CD-associated NOD2 variants p.Arg702Trp (rs2066844), p.Gly908Arg (rs2066847), and p.Leu1007fsX1008 (rs2066847). Haplotype and genotype-phenotype analyses were performed. The SNPs rs2066843 (p = 3.01×10−5, OR 1.48, [95% CI 1.23-1.78]) and rs2076756 (p = 4.01×10−6; OR 1.54, [95% CI 1.28-1.86]) were significantly associated with CD but not with UC susceptibility. Haplotype analysis revealed a number of significant associations with CD susceptibility with omnibus p values <10−10. The SNPs rs2066843 and rs2076756 were in linkage disequilibrium with each other and with the three main CD-associated NOD2 mutations (D''>0.9). However, in CD, SNPs rs2066843 and rs2076756 were more frequently observed than the other three common NOD2 mutations (minor allele frequencies for rs2066843 and rs2076756: 0.390 and 0.380, respectively). In CD patients homozygous for these novel NOD2 variants, genotype-phenotype analysis revealed higher rates of a penetrating phenotype (rs2076756: p = 0.015) and fistulas (rs2076756: p = 0.015) and significant associations with CD-related surgery (rs2076756: p = 0.003; rs2066843: p = 0.015). However, in multivariate analysis only disease localization (p<2×10−16) and behaviour (p = 0.02) were significantly associated with the need for surgery.Conclusion/Significance
The NOD2 variants rs2066843 and rs2076756 are novel and common CD susceptibility gene variants. 相似文献992.
993.
Krammer F Pontiller J Tauer C Palmberger D Maccani A Baumann M Grabherr R 《PloS one》2010,5(10):e13265
Recombinant protein expression in mammalian cells has become a very important technique over the last twenty years. It is mainly used for production of complex proteins for biopharmaceutical applications. Transient recombinant protein expression is a possible strategy to produce high quality material for preclinical trials within days. Viral replicon based expression systems have been established over the years and are ideal for transient protein expression. In this study we describe the evaluation of an influenza A replicon for the expression of recombinant proteins. We investigated transfection and expression levels in HEK-293 cells with EGFP and firefly luciferase as reporter proteins. Furthermore, we studied the influence of different influenza non-coding regions and temperature optima for protein expression as well. Additionally, we exploited the viral replication machinery for the expression of an antiviral protein, the human monoclonal anti-HIV-gp41 antibody 3D6. Finally we could demonstrate that the expression of a single secreted protein, an antibody light chain, by the influenza replicon, resulted in fivefold higher expression levels compared to the usually used CMV promoter based expression. We emphasize that the influenza A replicon system is feasible for high level expression of complex proteins in mammalian cells. 相似文献
994.
995.
Schiestl FP Steinebrunner F Schulz C von Reuss S Francke W Weymuth C Leuchtmann A 《Biology letters》2006,2(3):401-404
Fungi produce a plethora of secondary metabolites yet their biological significance is often little understood. Some compounds show well-known antibiotic properties, others may serve as volatile signals for the attraction of insects that act as vectors of spores or gametes. Our investigations in an outcrossing, self-incompatible fungus show that a fungus-produced volatile compound with fungitoxic activities is also responsible for the attraction of specific insects that transfer gametes. We argue that insect attraction using this compound is likely to have evolved from its primary function of defence--as has been suggested for floral scent in the angiosperms. We, thus, propose that similar yet convergent evolutionary pathways have lead to interspecific communication signals in both fungi and plants. 相似文献
996.
997.
Bringmann G Noll TF Gulder TA Grüne M Dreyer M Wilde C Pankewitz F Hilker M Payne GD Jones AL Goodfellow M Fiedler HP 《Nature chemical biology》2006,2(8):429-433
Metabolic diversity is being studied intensively by evolutionary biologists, but so far there has been no comparison of biosynthetic pathways leading to a particular secondary metabolite in both prokaryotes and eukaryotes. We have detected the bioactive anthraquinone chrysophanol, which serves as a chemical defense in diverse eukaryotic organisms, in a bacterial Nocardia strain, thereby permitting the first comparative biosynthetic study. Two basic modes of folding a polyketide chain to fused-ring aromatic structures have so far been described: mode F (referring to fungi) and mode S (from Streptomyces). We have demonstrated that in eukaryotes (fungi, higher plants and insects), chrysophanol is formed via folding mode F. In actinomycetes, by contrast, the cyclization follows mode S. Thus, chrysophanol is the first polyketide synthase product that is built up by more than one polyketide folding mode. 相似文献
998.
999.
Background
Inorganic polyphosphate (poly P) occurs universally in all organisms from bacteria to man. It functions, for example, as a phosphate and energy store, and is involved in the activation and regulation of proteins. Despite its ubiquitous occurrence and important functions, it is unclear how poly P is synthesized or how poly P metabolism is regulated in higher eukaryotes. This work describes a systematic analysis of poly P levels in yeast knockout strains mutated in almost every non-essential gene. 相似文献1000.
Stephan Waack Oliver Keller Roman Asper Thomas Brodag Carsten Damm Wolfgang Florian Fricke Katharina Surovcik Peter Meinicke Rainer Merkl 《BMC bioinformatics》2006,7(1):142-12