全文获取类型
收费全文 | 38988篇 |
免费 | 2527篇 |
国内免费 | 15篇 |
专业分类
41530篇 |
出版年
2023年 | 231篇 |
2022年 | 533篇 |
2021年 | 923篇 |
2020年 | 536篇 |
2019年 | 692篇 |
2018年 | 960篇 |
2017年 | 812篇 |
2016年 | 1338篇 |
2015年 | 2040篇 |
2014年 | 2170篇 |
2013年 | 2972篇 |
2012年 | 3400篇 |
2011年 | 3237篇 |
2010年 | 1979篇 |
2009年 | 1703篇 |
2008年 | 2419篇 |
2007年 | 2338篇 |
2006年 | 2072篇 |
2005年 | 1865篇 |
2004年 | 1752篇 |
2003年 | 1694篇 |
2002年 | 1533篇 |
2001年 | 318篇 |
2000年 | 220篇 |
1999年 | 306篇 |
1998年 | 381篇 |
1997年 | 256篇 |
1996年 | 255篇 |
1995年 | 231篇 |
1994年 | 226篇 |
1993年 | 222篇 |
1992年 | 136篇 |
1991年 | 146篇 |
1990年 | 148篇 |
1989年 | 109篇 |
1988年 | 101篇 |
1987年 | 91篇 |
1986年 | 71篇 |
1985年 | 95篇 |
1984年 | 97篇 |
1983年 | 72篇 |
1982年 | 85篇 |
1981年 | 80篇 |
1980年 | 79篇 |
1979年 | 74篇 |
1978年 | 39篇 |
1977年 | 50篇 |
1976年 | 36篇 |
1975年 | 38篇 |
1973年 | 43篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
91.
Nicola Pirastu Ciara McDonnell Eryk J. Grzeszkowiak Ninon Mounier Fumiaki Imamura Jordi Merino Felix R. Day Jie Zheng Nele Taba Maria Pina Concas Linda Repetto Katherine A. Kentistou Antonietta Robino Tnu Esko Peter K. Joshi Krista Fischer Ken K. Ong Tom R. Gaunt Zoltn Kutalik John R. B. Perry James F. Wilson 《PLoS genetics》2022,18(6)
Diet is considered as one of the most important modifiable factors influencing human health, but efforts to identify foods or dietary patterns associated with health outcomes often suffer from biases, confounding, and reverse causation. Applying Mendelian randomization in this context may provide evidence to strengthen causality in nutrition research. To this end, we first identified 283 genetic markers associated with dietary intake in 445,779 UK Biobank participants. We then converted these associations into direct genetic effects on food exposures by adjusting them for effects mediated via other traits. The SNPs which did not show evidence of mediation were then used for MR, assessing the association between genetically predicted food choices and other risk factors, health outcomes. We show that using all associated SNPs without omitting those which show evidence of mediation, leads to biases in downstream analyses (genetic correlations, causal inference), similar to those present in observational studies. However, MR analyses using SNPs which have only a direct effect on the exposure on food exposures provided unequivocal evidence of causal associations between specific eating patterns and obesity, blood lipid status, and several other risk factors and health outcomes. 相似文献
92.
93.
Harshad S. Ugamraj Kevin Dang Laure-Hlne Ouisse Benjamin Buelow Eduardo N. Chini Giulia Castello James Allison Starlynn C Clarke Laura M. Davison Roland Buelow Rong Deng Suhasini Iyer Ute Schellenberger Sankar N. Manika Shipra Bijpuria Astrid Musnier Anne Poupon Maria Cristina Cuturi Wim van Schooten Pranjali Dalvi 《MABS-AUSTIN》2022,14(1)
94.
95.
Paula Martínez Raúl Snchez-Vzquez Iole Ferrara-Romeo Rosa Serrano Juana M. Flores Maria A. Blasco 《PLoS genetics》2022,18(6)
The shelterin protein POT1 has been found mutated in many different familial and sporadic cancers, however, no mouse models to understand the pathobiology of these mutations have been developed so far. To address the molecular mechanisms underlying the tumorigenic effects of POT1 mutant proteins in humans, we have generated a mouse model for the human POT1R117C mutation found in Li-Fraumeni-Like families with cases of cardiac angiosarcoma by introducing this mutation in the Pot1a endogenous locus, knock-in for Pot1aR117C. We find here that both mouse embryonic fibroblasts (MEFs) and tissues from Pot1a+/ki mice show longer telomeres than wild-type controls. Longer telomeres in Pot1a+/ki MEFs are dependent on telomerase activity as they are not found in double mutant Pot1a+/ki Tert-/- telomerase-deficient MEFs. By using complementation assays we further show that POT1a pR117C exerts dominant-negative effects at telomeres. As in human Li-Fraumeni patients, heterozygous Pot1a+/ki mice spontaneously develop a high incidence of angiosarcomas, including cardiac angiosarcomas, and this is associated to the presence of abnormally long telomeres in endothelial cells as well as in the tumors. The Pot1a+/R117C mouse model constitutes a useful tool to understand human cancers initiated by POT1 mutations. 相似文献
96.
97.
Mustapha Arkoun Laëtitia Jannin Philippe Laîné Philippe Etienne Céline Masclaux-Daubresse Sylvie Citerne Maria Garnica José-Maria Garcia-Mina Jean-Claude Yvin Alain Ourry 《Plant and Soil》2013,362(1-2):79-92
Background and aims
Urea is the major nitrogen (N) form supplied as fertilizer in agriculture. However, urease, a nickel-dependent enzyme, allows plants to use external or internally generated urea as a nitrogen source. Since a urease inhibitor is frequently applied in conjunction with urea fertilizer, the N-metabolism of plants may be affected. The aim of this study was to determine physiological and molecular effects of nickel deficiency and a urease inhibitor on urea uptake and assimilation in oilseed rape.Methods
Plants were grown on hydroponic solution with urea as the sole N source under three treatments: plants treated with nickel (+Ni) as a control, without nickel (?Ni) and with nickel and phenylphosphorodiamidate (+Ni+PPD). Urea transport and assimilation were investigated.Results
The results show that Ni-deficiency or PPD supply led to reduced growth and reduced 15N-uptake from urea. This effect was more pronounced in PPD-treated plants, which accumulated high amounts of urea and ammonium. Thus, Ni-deficiency or addition of PPD, limit the availability of N and decreased shoot and root amino acid content. The up-regulation of BnDUR3 in roots indicated that this gene is a component of the stress response to nitrogen-deficiency. A general decline of glutamine synthetase (GS) activity and activation of glutamate dehydrogenase (GDH) and increases in its expression level were observed in control plants. At the same time, in (?N) or (+Ni+PPD) treated plants, no increases in GS or GDH activities and expression level were found.Conclusions
Overall results showed that plants require Ni as a nutrient (while most widely used nutrient solutions are devoid of Ni), whether they are grown with or without a urea supply, and that urease inhibitors may have deleterious effects at least in hydroponic grown oilseed rape. 相似文献98.
Loiselle DR Thelin WR Parker CE Dicheva NN Kesner BA Mocanu V Wang F Milgram SL Warren MR Borchers CH 《Journal of proteome research》2005,4(3):992-997
In this work, a method for improved protein identification of low-abundance proteins using unstained gels, in combination with robotics and matrix-assisted laser desorption/ionization tandem mass spectrometry, has been developed and evaluated. Omitting the silver-staining process resulted in increased protein identification scores, an increase in the number of peptides observed in the MALDI mass spectrum, and improved quality of the tandem mass spectrometry data. 相似文献
99.
The Role of Influenza A Virus Hemagglutinin Residues 226 and 228 in Receptor Specificity and Host Range Restriction 总被引:18,自引:8,他引:18 下载免费PDF全文
Angela Vines Krisna Wells Mikhail Matrosovich Maria R. Castrucci Toshihiro Ito Yoshihiro Kawaoka 《Journal of virology》1998,72(9):7626-7631
Influenza A viruses can be isolated from a variety of animals, but their range of hosts is restricted. For example, human influenza viruses do not replicate in duck intestine, the major replication site of avian viruses in ducks. Although amino acids at positions 226 and 228 of hemagglutinin (HA) of the H3 subtype are known to be important for this host range restriction, the contributions of specific amino acids at these positions to restriction were not known. Here, we address this issue by generating HAs with site-specific mutations of a human virus that contain different amino acid residues at these positions. We also let ducks select replication-competent viruses from a replication-incompetent virus containing a human virus HA by inoculating animals with 1010.5 50% egg infectious dose of the latter virus and identified a mutation in the HA. Our results showed that the Ser-to-Gly mutation at position 228, in addition to the Leu-to-Gln mutation at position 226 of the HA of the H3 subtype, is critical for human virus HA to support virus replication in duck intestine. 相似文献
100.
MH Daleke AD van der Woude AH Parret R Ummels AM de Groot D Watson SR Piersma CR Jiménez J Luirink W Bitter EN Houben 《The Journal of biological chemistry》2012,287(38):31939-31947
Mycobacteria use the dedicated type VII protein secretion systems ESX-1 and ESX-5 to secrete virulence factors across their highly hydrophobic cell envelope. The substrates of these systems include the large mycobacterial PE and PPE protein families, which are named after their characteristic Pro-Glu and Pro-Pro-Glu motifs. Pathogenic mycobacteria secrete large numbers of PE/PPE proteins via the major export pathway, ESX-5. In addition, a few PE/PPE proteins have been shown to be exported by ESX-1. It is not known how ESX-1 and ESX-5 recognize their cognate PE/PPE substrates. In this work, we investigated the function of the cytosolic protein EspG(5), which is essential for ESX-5-mediated secretion in Mycobacterium marinum, but for which the role in secretion is not known. By performing protein co-purifications, we show that EspG(5) interacts with several PPE proteins and a PE/PPE complex that is secreted by ESX-5, but not with the unrelated ESX-5 substrate EsxN or with PE/PPE proteins secreted by ESX-1. Conversely, the ESX-1 paralogue EspG(1) interacted with a PE/PPE couple secreted by ESX-1, but not with PE/PPE substrates of ESX-5. Furthermore, structural analysis of the complex formed by EspG(5) and PE/PPE indicates that these proteins interact in a 1:1:1 ratio. In conclusion, our study shows that EspG(5) and EspG(1) interact specifically with PE/PPE proteins that are secreted via their own ESX systems and suggests that EspG proteins are specific chaperones for the type VII pathway. 相似文献