全文获取类型
收费全文 | 2449篇 |
免费 | 170篇 |
专业分类
2619篇 |
出版年
2024年 | 3篇 |
2023年 | 21篇 |
2022年 | 39篇 |
2021年 | 85篇 |
2020年 | 50篇 |
2019年 | 57篇 |
2018年 | 77篇 |
2017年 | 48篇 |
2016年 | 104篇 |
2015年 | 157篇 |
2014年 | 207篇 |
2013年 | 211篇 |
2012年 | 243篇 |
2011年 | 245篇 |
2010年 | 149篇 |
2009年 | 122篇 |
2008年 | 158篇 |
2007年 | 145篇 |
2006年 | 108篇 |
2005年 | 106篇 |
2004年 | 82篇 |
2003年 | 75篇 |
2002年 | 66篇 |
2001年 | 9篇 |
2000年 | 5篇 |
1999年 | 12篇 |
1998年 | 13篇 |
1997年 | 6篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1984年 | 1篇 |
排序方式: 共有2619条查询结果,搜索用时 7 毫秒
71.
Justin Clark Austen Terwilliger Chinh Nguyen Sabrina Green Chris Nobles Anthony Maresso 《Molecular microbiology》2019,112(2):515-531
A challenge common to all bacterial pathogens is to acquire nutrients from hostile host environments. Iron is an important cofactor required for essential cellular processes such as DNA repair, energy production and redox balance. Within a mammalian host, most iron is sequestered within heme, which in turn is predominantly bound by hemoglobin. While little is understood about the mechanisms by which bacterial hemophores attain heme from host‐hemoglobin, even less is known about intracellular heme processing. Bacillus anthracis, the causative agent of anthrax, displays a remarkable ability to grow in mammalian hosts. Hypothesizing this pathogen harbors robust ways to catabolize heme, we characterize two new intracellular heme‐binding proteins that are distinct from the previously described IsdG heme monooxygenase. The first of these, HmoA, binds and degrades heme, is necessary for heme detoxification and facilitates growth on heme iron sources. The second protein, HmoB, binds and degrades heme too, but is not necessary for heme utilization or virulence. The loss of both HmoA and IsdG renders B. anthracis incapable of causing anthrax disease. The additional loss of HmoB in this background increases clearance of bacilli in lungs, which is consistent with this protein being important for survival in alveolar macrophages. 相似文献
72.
Word Sense Disambiguation (WSD) is the task of determining which sense of an ambiguous word (word with multiple meanings) is chosen in a particular use of that word, by considering its context. A sentence is considered ambiguous if it contains ambiguous word(s). Practically, any sentence that has been classified as ambiguous usually has multiple interpretations, but just one of them presents the correct interpretation. We propose an unsupervised method that exploits knowledge based approaches for word sense disambiguation using Harmony Search Algorithm (HSA) based on a Stanford dependencies generator (HSDG). The role of the dependency generator is to parse sentences to obtain their dependency relations. Whereas, the goal of using the HSA is to maximize the overall semantic similarity of the set of parsed words. HSA invokes a combination of semantic similarity and relatedness measurements, i.e., Jiang and Conrath (jcn) and an adapted Lesk algorithm, to perform the HSA fitness function. Our proposed method was experimented on benchmark datasets, which yielded results comparable to the state-of-the-art WSD methods. In order to evaluate the effectiveness of the dependency generator, we perform the same methodology without the parser, but with a window of words. The empirical results demonstrate that the proposed method is able to produce effective solutions for most instances of the datasets used. 相似文献
73.
Andreas Hartmann Julia Muellner Niklaus Meier Helke Hesekamp Priscilla van Meerbeeck Marie-Odile Habert Aurélie Kas Marie-Laure Tanguy Merry Mazmanian Hervé Oya Nissen Abuaf Hafida Gaouar Sabrina Salhi Fanny Charbonnier-Beaupel Marie-Hélène Fievet Damien Galanaud Sophie Arguillere Emmanuel Roze Bertrand Degos David Grabli Lucette Lacomblez Cécile Hubsch Marie Vidailhet Anne-Marie Bonnet Jean-Christophe Corvol Michael Schüpbach 《PloS one》2016,11(9)
74.
Sabrina Rasheed A. K. Siddique Tamanna Sharmin A. M. R. Hasan S. M. A. Hanifi M. Iqbal Abbas Bhuiya 《PloS one》2016,11(4)
BackgroundHigh salt consumption is an important risk factor of elevated blood pressure. In Bangladesh about 20 million people are at high risk of hypertension due to climate change induced saline intrusion in water. The objective of this study is to assess beliefs, perceptions, and practices associated with salt consumption in coastal Bangladesh.MethodsThe study was conducted in Chakaria, Bangladesh between April-June 2011. It was a cross sectional mixed method study. For the qualitative study 6 focus group discussions, 8 key informant interviews, 60 free listing exercises, 20 ranking exercises and 10 observations were conducted. 400 adults were randomly selected for quantitative survey. For analysis we used SPSS for quantitative data, and Anthropac and Nvivo for qualitative data.ResultsSalt was described as an essential component of food with strong cultural and religious roots. People described both health benefits and risks related to salt intake. The overall risk perception regarding excessive salt consumption was low and respondents believed that the cooking process can render the salt harmless. Respondents were aware that salt is added in many foods even if they do not taste salty but did not recognize that salt can occur naturally in both foods and water.ConclusionsIn the study community people had low awareness of the risks associated with excess salt consumption and salt reduction strategies were not high in their agenda. The easy access to and low cost of salt as well as unrecognised presence of salt in drinking water has created an environment conducive to excess salt consumption. It is important to design general messages related to salt reduction and test tailored strategies especially for those at high risk of hypertension. 相似文献
75.
Sabrina Nickel Farnusch Kaschani Tom Colby Renier A.L. van der Hoorn Markus Kaiser 《Bioorganic & medicinal chemistry》2012,20(2):601-606
Activity-based protein profiling represents a powerful methodology to probe the activity state of enzymes under various physiological conditions. Here we present the development of a para-nitrophenol phosphonate activity-based probe with structural similarities to the potent agrochemical paraoxon. We demonstrate that this probes labels distinct serine hydrolases with the carboxylesterase CXE12 as the predominant target in Arabidopsis thaliana. The designed probe features a distinct labeling pattern and therefore represents a promising chemical tool to investigate physiological roles of selected serine hydrolases such as CXE12 in plant biology. 相似文献
76.
Riccardo Baroncelli Antonio Zapparata Sabrina Sarrocco Serenella A. Sukno Charles R. Lane Michael R. Thon Giovanni Vannacci Eric Holub Surapareddy Sreenivasaprasad 《PloS one》2015,10(6)
Fragaria × ananassa (common name: strawberry) is a globally cultivated hybrid species belonging to Rosaceae family. Colletotrichum acutatum sensu lato (s.l.) is considered to be the second most economically important pathogen worldwide affecting strawberries. A collection of 148 Colletotrichum spp. isolates including 67 C. acutatum s.l. isolates associated with the phytosanitary history of UK strawberry production were used to characterize multi-locus genetic variation of this pathogen in the UK, relative to additional reference isolates that represent a worldwide sampling of the diversity of the fungus. The evidence indicates that three different species C. nymphaeae, C. godetiae and C. fioriniae are associated with strawberry production in the UK, which correspond to previously designated genetic groups A2, A4 and A3, respectively. Among these species, 12 distinct haplotypes were identified suggesting multiple introductions into the country. A subset of isolates was also used to compare aggressiveness in causing disease on strawberry plants and fruits. Isolates belonging to C. nymphaeae, C. godetiae and C. fioriniae representative of the UK anthracnose pathogen populations showed variation in their aggressiveness. Among the three species, C. nymphaeae and C. fioriniae appeared to be more aggressive compared to C. godetiae. This study highlights the genetic and pathogenic heterogeneity of the C. acutatum s.l. populations introduced into the UK linked to strawberry production. 相似文献
77.
de Carvalho SC Martins Junior Ade J Lima JB Valle D 《Memórias do Instituto Oswaldo Cruz》2002,97(8):1117-1120
Temperature influence on the embryonic development of Anopheles aquasalis and An. albitarsis was investigated. At 26 degrees C, 75% and 60% of respectively An. aquasalis and An. albitarsis eggs hatched, with one peak of eclosion, between the 2nd and 3rd day after oviposition. At 20 +/- 2 degrees C, around 66-70% of An. aquasalis eggs hatched, with one eclosion peak, on the 5th day. On the other hand, An. albitarsis eclosion at 21+/- 2 degrees C decreased to 10-22%, with two eclosion peaks, on the 4th-5th day and on the 9th-12th day. These data indicate a stronger temperature influence over An.albitarsis than over An. aquasalis embryos. 相似文献
78.
Michele Tonelli Matteo Simone Bruno Tasso Federica Novelli Vito Boido Fabio Sparatore Giuseppe Paglietti Sabrina Pricl Gabriele Giliberti Sylvain Blois Cristina Ibba Giuseppina Sanna Roberta Loddo Paolo La Colla 《Bioorganic & medicinal chemistry》2010,18(8):2937-2953
Seventy-six 2-phenylbenzimidazole derivatives were synthesized and evaluated in cell-based assays for cytotoxicity and antiviral activity against a panel of 10 RNA and DNA viruses. The most commonly affected viruses were, in decreasing order, CVB-2, BVDV, Sb-1, HSV-1, and YFV, while HIV-1 and VSV were not affected, and RSV, VV and Reo-1 were only susceptible to a few compounds. Thirty-nine compounds exhibited high activity (EC50 = 0.1–10 μM) against at least one virus, and four of them were outstanding for their high and selective activity against VV (24, EC50 = 0.1 μM) and BVDV (50, 51, and 53 with EC50 = 1.5, 0.8, and 1.0 μM, respectively). The last compounds inhibited at low micromolar concentrations the NS5B RdRp of BVDV and also of HCV, the latter sharing structural similarity with the former. The considered compounds represent attractive leads for the development of antiviral agents against poxviruses, pestiviruses and even HCV, which are important human and veterinary pathogens. 相似文献
79.
Didac Carmona-Gutierrez Ali Alavian-Ghavanini Lukas Habernig Maria Anna Bauer Astrid Hammer Christine Rossmann Andreas S. Zimmermann Christoph Ruckenstuhl Sabrina Büttner Tobias Eisenberg Wolfgang Sattler Ernst Malle Frank Madeo 《Cell cycle (Georgetown, Tex.)》2013,12(11):1704-1712
Following microbial pathogen invasion, the human immune system of activated phagocytes generates and releases the potent oxidant hypochlorous acid (HOCl), which contributes to the killing of menacing microorganisms. Though tightly controlled, HOCl generation by the myeloperoxidase-hydrogen peroxide-chloride system of neutrophils/monocytes may occur in excess and lead to tissue damage. It is thus of marked importance to delineate the molecular pathways underlying HOCl cytotoxicity in both microbial and human cells. Here, we show that HOCl induces the generation of reactive oxygen species (ROS), apoptotic cell death and the formation of specific HOCl-modified epitopes in the budding yeast Saccharomyces cerevisiae. Interestingly, HOCl cytotoxicity can be prevented by treatment with ROS scavengers, suggesting oxidative stress to mediate the lethal effect. The executing pathway involves the pro-apoptotic protease Kex1p, since its absence diminishes HOCl-induced production of ROS, apoptosis and protein modification. By characterizing HOCl-induced cell death in yeast and identifying a corresponding central executor, these results pave the way for the use of Saccharomyces cerevisiae in HOCl research, not least given that it combines both being a microorganism as well as a model for programmed cell death in higher eukaryotes. 相似文献