全文获取类型
收费全文 | 3057篇 |
免费 | 152篇 |
国内免费 | 1篇 |
专业分类
3210篇 |
出版年
2024年 | 4篇 |
2023年 | 18篇 |
2022年 | 50篇 |
2021年 | 67篇 |
2020年 | 45篇 |
2019年 | 58篇 |
2018年 | 71篇 |
2017年 | 70篇 |
2016年 | 125篇 |
2015年 | 170篇 |
2014年 | 221篇 |
2013年 | 217篇 |
2012年 | 262篇 |
2011年 | 241篇 |
2010年 | 168篇 |
2009年 | 138篇 |
2008年 | 187篇 |
2007年 | 171篇 |
2006年 | 127篇 |
2005年 | 120篇 |
2004年 | 126篇 |
2003年 | 90篇 |
2002年 | 83篇 |
2001年 | 74篇 |
2000年 | 68篇 |
1999年 | 43篇 |
1998年 | 16篇 |
1997年 | 14篇 |
1996年 | 14篇 |
1995年 | 7篇 |
1994年 | 4篇 |
1993年 | 5篇 |
1992年 | 15篇 |
1991年 | 12篇 |
1990年 | 11篇 |
1989年 | 14篇 |
1988年 | 9篇 |
1987年 | 6篇 |
1986年 | 6篇 |
1985年 | 9篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 6篇 |
1979年 | 9篇 |
1978年 | 4篇 |
1975年 | 4篇 |
1974年 | 5篇 |
1973年 | 4篇 |
1972年 | 3篇 |
1968年 | 2篇 |
排序方式: 共有3210条查询结果,搜索用时 0 毫秒
381.
Ho Joong Sung Mee Kyung Jung Yong-Bin Eom Jong-Eun Lee Jae Woong Sull Sun Ha Jee 《Genes & genomics.》2012,34(1):103-106
Fasting glucose level is the most basic and widely used indicator of diabetes. Several genome wide association studies have reported that the gene encoding melatonin receptor 1B (MTNR1B) exerts a major effect on serum fasting glucose levels. We tested for the association between single nucleotide polymorphisms (SNPs) in the MTNR1B gene and fasting glucose levels in a Korean population consisting of 8,229 subjects taken from two community-based cohorts. The mean age of the subjects in the study population was 51.9 years. For this study, we selected 363 SNPs located in the MTNR1B gene, which is located on chromosome 11. Multivariate linear regression models were used to test for genotypic effects on fasting glucose levels while adjusting for age and sex under an additive model. The MTNR1B SNP most highly associated with fasting glucose levels was rs10830962 (p=1.95×10?5), followed by rs3847554 (p=3.16×10?4). Replication of these initial findings is important to better understand the correlation between MTNR1B variations and their effects, especially in Asian populations. 相似文献
382.
Ha GH Kim HS Go H Lee H Seimiya H Chung DH Lee CW 《Cell death and differentiation》2012,19(2):321-332
Telomere length is critical for chromosome stability that affects cell proliferation and survival. Telomere elongation by telomerase is inhibited by the telomeric protein, TRF1. Tankyrase-1 (TNKS1) poly(ADP-ribosyl)ates TRF1 and releases TRF1 from telomeres, thereby allowing access of telomerase to the telomeres. TNKS1-mediated poly(ADP-ribosyl)ation also appears to be crucial for regulating the mitotic cell cycle. In searching for proteins that interact with polo-like kinase-1 (Plk1) by using complex proteomics, we identified TNKS1 as a novel Plk1-binding protein. Here, we report that Plk1 forms a complex with TNKS1 in vitro and in vivo, and phosphorylates TNKS1. Phosphorylation of TNKS1 by Plk1 appears to increase TNKS1 stability and telomeric poly(ADP-ribose) polymerase (PARP) activity. By contrast, targeted inhibition of Plk1 or mutation of phosphorylation sites decreased the stability and PARP activity of TNKS1, leading to distort mitotic spindle-pole assembly and telomeric ends. Taken together, our results provide evidence of a novel molecular mechanism in which phosphorylation of TNKS1 by Plk1 may help regulate mitotic spindle assembly and promote telomeric chromatin maintenance. 相似文献
383.
Kim RN Kim DS Choi SH Yoon BH Kang A Nam SH Kim DW Kim JJ Ha JH Toyoda A Fujiyama A Kim A Kim MY Park KH Lee KS Park HS 《DNA research》2012,19(3):275-287
Although pioneering sequencing projects have shed light on the boxer and poodle genomes, a number of challenges need to be met before the sequencing and annotation of the dog genome can be considered complete. Here, we present the DNA sequence of the Jindo dog genome, sequenced to 45-fold average coverage using Illumina massively parallel sequencing technology. A comparison of the sequence to the reference boxer genome led to the identification of 4 675 437 single nucleotide polymorphisms (SNPs, including 3 346 058 novel SNPs), 71 642 indels and 8131 structural variations. Of these, 339 non-synonymous SNPs and 3 indels are located within coding sequences (CDS). In particular, 3 non-synonymous SNPs and a 26-bp deletion occur in the TCOF1 locus, implying that the difference observed in cranial facial morphology between Jindo and boxer dogs might be influenced by those variations. Through the annotation of the Jindo olfactory receptor gene family, we found 2 unique olfactory receptor genes and 236 olfactory receptor genes harbouring non-synonymous homozygous SNPs that are likely to affect smelling capability. In addition, we determined the DNA sequence of the Jindo dog mitochondrial genome and identified Jindo dog-specific mtDNA genotypes. This Jindo genome data upgrade our understanding of dog genomic architecture and will be a very valuable resource for investigating not only dog genetics and genomics but also human and dog disease genetics and comparative genomics. 相似文献
384.
385.
Anthony Kwasiborski Mohammed Bajji Pierre Delaplace Patrick du Jardin Ha?ssam M. Jijakli 《BioControl》2012,57(6):837-848
The biocontrol by Pichia anomala strain Kh6 (Hansen) Kurtzman (Saccharomycetales: Endomycetaceae) has been extensively studied using microbial, biochemical and molecular approaches. However, due to the complexity of the interaction process, the inhibition mechanism remains uncharacterized. An objective study based on proteomic techniques could allow to increase our knowledge. Studying modes of action requires conditions as close as possible to natural infection in order to take into account interactions between organisms implicating a more complex protein extraction procedure. In the present study, we developed an in situ model allowing the interaction between apple, antagonist and pathogen and maintaining the antagonist inhibitory effect while limiting the contaminations by the apple components. Moreover, we set up an extraction protocol compatible with our in situ conditions and suitable for 2D analysis. Nine protocols, which differed in cell lysis or protein precipitation procedures, were compared on the basis of the protein yield, 1D gel quality and 2D gel quality. 相似文献
386.
Nam HJ Kang JK Chang JS Lee MS Nam ST Jung HW Kim SK Ha EM Seok H Son SW Park YJ Kim H 《Journal of microbiology and biotechnology》2012,22(1):50-57
Phospholipase C-γl (PLC-γl) expression is associated with cellular transformation. Notably, PLC-gamma is up-regulated in colorectal cancer tissue and breast carcinoma. Because exotoxins released by Clostridium botulinum have been shown to induce apoptosis and promote growth arrest in various cancer cell lines, we examined here the potential of Clostridium difficile toxin A to selectively induce apoptosis in cells transformed by PLC-γl overexpression. We found that PLC-γl-transformed cells, but not vectortransformed (control) cells, were highly sensitive to C. difficile toxin A-induced apoptosis and mitotic inhibition. Moreover, expression of the proapoptotic Bcl2 family member, Bim, and activation of caspase-3 were significantly up-regulated by toxin A in PLC-γl-transformed cells. Toxin A-induced cell rounding and paxillin dephosphorylation were also significantly higher in PLC-γl-transformed cells than in control cells. These findings suggest that C. difficile toxin A may have potential as an anticancer agent against colorectal cancers and breast carcinomas in which PLC-γl is highly up-regulated. 相似文献
387.
We studied the role of a RhoA-specific guanine nucleotide exchange factor (p190RhoGEF) in dendritic cells (DCs), using transgenic (TG) mice that over-express a full gene of p190RhoGEF under the control of an invariant chain promoter. TG mice lacked localization of activated DCs to the T cell zone in the spleen and had reduced serum levels of IL-6 in response to lipopolysaccharide (LPS) injection. DCs from these mice also showed reduced surface expression of CD86, CD40, and CD205, but not MHCII, as well as a reduced capability to uptake antigen. Moreover, chemokine-driven migration and secretion of IL-6, but not of IL-12, were impaired after LPS-stimulation of TG DCs. Collectively, these results suggest that over-expressing p190RhoGEF negatively regulates conventional DC function in response to bacterial LPS infection. 相似文献
388.
Oleg Bol'shakov Judit Kovacs Mamta Chahar Khanh Ha Levan Khelashvili Alan R. Katritzky 《Journal of peptide science》2012,18(11):704-709
S‐Acyl cysteine peptides containing α‐, β‐ or γ‐amino acid residues undergo long‐range S‐ to N‐acyl transfer to give analogs of native tripeptides and tetrapeptides containing additional carbon atoms in the chain. The ease of intramolecular S → N‐acyl transfer relative to intermolecular transacylation is favored increasingly for 9 < 12 < 13 ~ 10‐membered cyclic transition states; the observed order is explained on conformational and intermolecular interaction considerations. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
389.
Cho MS Lee JH Her NH Kim C Seol YJ Hahn JH Baeg JH Kim HG Park DS 《Journal of microbiology (Seoul, Korea)》2012,50(3):496-501
The Gram-positive bacterium Clavibacter michiganensis subsp. michiganensis is the causal agent of canker disease in tomato. Because it is very important to control newly introduced inoculum sources from commercial materials, the specific detection of this pathogen in seeds and seedlings is essential for effective disease control. In this study, a novel and efficient assay for the detection and quantitation of C. michiganensis subsp. michiganensis in symptomless tomato and red pepper seeds was developed. A pair of polymerase chain reaction (PCR) primers (Cmm141F/R) was designed to amplify a specific 141 bp fragment on the basis of a ferredoxin reductase gene of C. michiganensis subsp. michiganensis NCPPB 382. The specificity of the primer set was evaluated using purified DNA from 16 isolates of five C. michiganensis subspecies, one other Clavibacter species, and 17 other reference bacteria. The primer set amplified a single band of expected size from the genomic DNA obtained from the C. michiganensis subsp. michiganensis strains but not from the other C. michiganensis subspecies or from other Clavibacter species. The detection limit was a single cloned copy of the ferredoxin reductase gene of C. michiganensis subsp. michiganensis. In conclusion, this quantitative direct PCR assay can be applied as a practical diagnostic method for epidemiological research and the sanitary management of seeds and seedlings with a low level or latent infection of C. michiganensis subsp. michiganensis. 相似文献
390.
Y Chan DC Lacap MC Lau KY Ha KA Warren-Rhodes CS Cockell DA Cowan CP McKay SB Pointing 《Environmental microbiology》2012,14(9):2272-2282
Drylands are the largest terrestrial biome on Earth and a ubiquitous feature is desert pavement terrain, comprising rocks embedded in the mineral soil surface. Quartz and other translucent rocks are common and microbial communities termed hypoliths develop as biofilms on their ventral surfaces. In extreme deserts these represent major concentrations of biomass, and are emerging as key to geobiological processes and soil stabilization. These highly specialized communities are dominated by cyanobacteria that support diverse heterotrophic assemblages. Here we identify global-scale trends in the ecology of hypoliths that are strongly related to climate, particularly with regard to shifts in cyanobacterial assemblages. A synthesis of available data revealed a linear trend for colonization with regard to climate, and we suggest potential application for hypoliths as 'biomarkers' of aridity on a landscape scale. The potential to exploit the soil-stabilizing properties of hypolithic colonization in environmental engineering on dryland soils is also discussed. 相似文献