全文获取类型
收费全文 | 22075篇 |
免费 | 1512篇 |
国内免费 | 9篇 |
专业分类
23596篇 |
出版年
2024年 | 19篇 |
2023年 | 127篇 |
2022年 | 313篇 |
2021年 | 580篇 |
2020年 | 352篇 |
2019年 | 472篇 |
2018年 | 594篇 |
2017年 | 480篇 |
2016年 | 812篇 |
2015年 | 1228篇 |
2014年 | 1344篇 |
2013年 | 1669篇 |
2012年 | 1958篇 |
2011年 | 1904篇 |
2010年 | 1179篇 |
2009年 | 1021篇 |
2008年 | 1387篇 |
2007年 | 1294篇 |
2006年 | 1183篇 |
2005年 | 1094篇 |
2004年 | 985篇 |
2003年 | 931篇 |
2002年 | 758篇 |
2001年 | 123篇 |
2000年 | 108篇 |
1999年 | 139篇 |
1998年 | 126篇 |
1997年 | 117篇 |
1996年 | 90篇 |
1995年 | 87篇 |
1994年 | 91篇 |
1993年 | 88篇 |
1992年 | 53篇 |
1991年 | 61篇 |
1990年 | 67篇 |
1989年 | 46篇 |
1988年 | 53篇 |
1987年 | 39篇 |
1986年 | 43篇 |
1985年 | 51篇 |
1984年 | 39篇 |
1983年 | 47篇 |
1982年 | 32篇 |
1981年 | 42篇 |
1980年 | 26篇 |
1979年 | 38篇 |
1978年 | 32篇 |
1977年 | 30篇 |
1976年 | 26篇 |
1975年 | 24篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
101.
RAM, a gene of yeast required for a functional modification of RAS proteins and for production of mating pheromone a-factor 总被引:46,自引:0,他引:46
We have identified a gene (SUPH) of S. cerevisiae that is required for both RAS function and mating by cells of a mating type. supH is allelic to ste16, a gene required for the production of the mating pheromone a-factor. Both RAS and a-factor coding sequences terminate with the potential acyltransferase recognition sequence Cys-A-A-X, where A is an aliphatic amino acid. Mutations in SUPH-STE16 prevent the membrane localization and maturation of RAS protein, as well as the fatty acid acylation of it and other membrane proteins. We propose the designation RAM (RAS protein and a-factor maturation function) for SUPH and STE16. RAM may encode an enzyme responsible for the modification and membrane localization of proteins with this C-terminal sequence. 相似文献
102.
Acinetobacter baumannii causes serious infections especially in immunocompromised and/or hospitalized patients. Several A. baumannii strains are multidrug resistant and infect wounds, bones, and the respiratory tract. Current studies are focused on finding new effective agents against A. baumannii. Phage therapy is a promising means to fight this bacterium and many studies on procuring and applying new phages against A. baumannii are currently being conducted. As shown in animal models, phages against multidrug-resistant A. baumannii may control bacterial infections caused by this pathogen and may be a real hope to solve this dangerous health problem. 相似文献
103.
The diploid Mexican species S. bulbocastanum (blb) was used as a source of late blight resistance in somatic hybridization with the potato (S. tuberosum, tbr) dihaploid H-8105. The produced 2x blb (+) 2x tbr H-8105 somatic hybrids did not retain the blb parent's characteristic high resistance to P. infestans. The revealed aneuploidy of blb (+) tbr H-8105 hybrids indicated a possible loss of individual blb chromosome(s) carrying the resistance genes. Four hybrid clones differing in terms of their ploidy, morphology and growth potential were analysed for the presence of all twelve blb chromosomes (linkage groups). The RAPD markers assigned to particular chromosomes were selected on the basis of the linkage map of S. bulbocastanum constructed by Naess et al., Mol. Gen. Genom. 265 (2001) 694-704. Of the 86 markers analysed, twelve (14%) were common for blb and H-8105, while 34 (40%) and 40 (46%) markers were specific for the blb and H-8105 genome, respectively; this confirms the differences between the nuclear genomes of the two species. Seventeen markers (20%) present in one or the other parent were absent in the hybrids, and only one new marker was found in the hybrids. The poorly growing, aneuploid and chimeric hybrids had the same band profiles as the well growing, morphologically normal hybrids, except for two bands that were present only in normal hybrids. The presence of eleven blb linkage groups in the blb (+) tbr H-8105 hybrids was confirmed. The markers specific for the second linkage group (chromosome 2) of blb were not present in the RAPD patterns of the somatic hybrids analysed, suggesting a loss or rearrangement of this chromosome in the combined nuclear genome of the hybrids. 相似文献
104.
Linda H Münger Mar Garcia-Aloy Rosa Vázquez-Fresno Doreen Gille Albert Remus R Rosana Anna Passerini María-Trinidad Soria-Florido Grégory Pimentel Tanvir Sajed David S Wishart Cristina Andres Lacueva Guy Vergères Giulia Praticò 《Genes & nutrition》2018,13(1):26
Dairy and egg products constitute an important part of Western diets as they represent an excellent source of high-quality proteins, vitamins, minerals and fats. Dairy and egg products are highly diverse and their associations with a range of nutritional and health outcomes are therefore heterogeneous. Such associations are also often weak or debated due to the difficulty in establishing correct assessments of dietary intake. Therefore, in order to better characterize associations between the consumption of these foods and health outcomes, it is important to identify reliable biomarkers of their intake. Biomarkers of food intake (BFIs) provide an accurate measure of intake, which is independent of the memory and sincerity of the subjects as well as of their knowledge about the consumed foods. We have, therefore, conducted a systematic search of the scientific literature to evaluate the current status of potential BFIs for dairy products and BFIs for egg products commonly consumed in Europe. Strikingly, only a limited number of compounds have been reported as markers for the intake of these products and none of them have been sufficiently validated. A series of challenges hinders the identification and validation of BFI for dairy and egg products, in particular, the heterogeneous composition of these foods and the lack of specificity of the markers identified so far. Further studies are, therefore, necessary to validate these compounds and to discover new candidate BFIs. Untargeted metabolomic strategies may allow the identification of novel biomarkers, which, when taken separately or in combination, could be used to assess the intake of dairy and egg products. 相似文献
105.
106.
Vera A González-Montalbán N Arís A Villaverde A 《Biotechnology and bioengineering》2007,96(6):1101-1106
Protein aggregation is a major bottleneck during the bacterial production of recombinant proteins. In general, the induction of gene expression at sub-optimal growth temperatures improves the solubility of aggregation-prone polypeptides and minimizes inclusion body (IB) formation. However, the effect of low temperatures on the quality of the recombinant protein, especially within the insoluble cell fraction, has been hardly ever explored. In this work, we have examined the conformational status of a recombinant GFP protein when produced in Escherichia coli below 37 degrees C. As expected, the fraction of aggregated protein largely decreased at lower temperatures, while the conformational quality of both soluble and aggregated GFP, as reflected by its specific fluorescence emission, progressively improved. This observation indicates that physicochemical conditions governing protein folding affect concurrently the quality of the soluble and the aggregated forms of a misfolding-prone protein, and that protein misfolding and aggregation are clearly not coincident events. 相似文献
107.
Seki N Toh U Kawaguchi K Ninomiya M Koketsu M Watanabe K Aoki M Fujii T Nakamura A Akagi Y Kusukawa J Kage M Shirouzu K Yamana H 《Journal of cellular biochemistry》2012,113(7):2346-2355
4',5,7-Trihydroxy-3',5'-dimethoxyflavone (Tricin), a naturally occurring flavone, has anti-inflammatory potential and exhibits diverse biological activities including antigrowth activity in several human cancer cell lines and cancer chemopreventive effects in the gastrointestinal tract of mice. The present study aimed to investigate the biological actions of tricin on hepatic stellate cells (HSCs) in vitro, exploring its potential as a treatment of liver fibrosis, since HSC proliferation is closely related to the progression of hepatic fibrogenesis in chronic liver diseases leading to irreversible liver cirrhosis and hepatocellular carcinoma. Tricin inhibited platelet-derived growth factor (PDGF)-BB-induced cell proliferation by blocking cell cycle progression and cell migration in the human HSC line LI90 and culture-activated HSCs. It also reduced the phosphorylation of PDGF receptor β and the downstream signaling molecules ERK1/2 and Akt, which might be due to its tyrosine kinase inhibitor properties rather than inhibition of the direct binding between PDGF-BB and its receptor. Our findings suggest that tricin might be beneficial in HSC-targeting therapeutic or chemopreventive applications for hepatic fibrosis. 相似文献
108.
Insulation and wiring specificity of BceR‐like response regulators and their target promoters in Bacillus subtilis 下载免费PDF全文
Chong Fang Anna Nagy‐Staroń Martin Grafe Ralf Heermann Kirsten Jung Susanne Gebhard Thorsten Mascher 《Molecular microbiology》2017,104(1):16-31
BceRS and PsdRS are paralogous two‐component systems in Bacillus subtilis controlling the response to antimicrobial peptides. In the presence of extracellular bacitracin and nisin, respectively, the two response regulators (RRs) bind their target promoters, PbceA or PpsdA, resulting in a strong up‐regulation of target gene expression and ultimately antibiotic resistance. Despite high sequence similarity between the RRs BceR and PsdR and their known binding sites, no cross‐regulation has been observed between them. We therefore investigated the specificity determinants of PbceA and PpsdA that ensure the insulation of these two paralogous pathways at the RR–promoter interface. In vivo and in vitro analyses demonstrate that the regulatory regions within these two promoters contain three important elements: in addition to the known (main) binding site, we identified a linker region and a secondary binding site that are crucial for functionality. Initial binding to the high‐affinity, low‐specificity main binding site is a prerequisite for the subsequent highly specific binding of a second RR dimer to the low‐affinity secondary binding site. In addition to this hierarchical cooperative binding, discrimination requires a competition of the two RRs for their respective binding site mediated by only slight differences in binding affinities. 相似文献
109.
Anna A Bencsik Anthony W Coleman Sabine O S Debeer Hervé Perron Aly Moussa 《The journal of histochemistry and cytochemistry》2006,54(8):849-853
Due to its sensitivity, immunohistochemistry (IHC) of abnormal prion protein (PrPsc) is used to study experimental and natural cases of transmissible spongiform encephalopathies (TSEs) such as Creutzfeldt-Jakob disease in humans or scrapie and bovine spongiform encephalopathy (BSE) in animals. The limits of detection are particularly critical when PrPsc IHC is used for diagnostic purposes. In this article, we describe for the first time the use of streptomycin sulfate in IHC, providing a novel original and easy way to amplify specifically PrPsc immunohistochemical detection in natural cases of BSE and scrapie, as well as in experimental TSEs in mice models using two different PrP antibodies. 相似文献
110.
Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21 总被引:3,自引:0,他引:3
Kurosu H Choi M Ogawa Y Dickson AS Goetz R Eliseenkova AV Mohammadi M Rosenblatt KP Kliewer SA Kuro-o M 《The Journal of biological chemistry》2007,282(37):26687-26695