全文获取类型
收费全文 | 5225篇 |
免费 | 460篇 |
国内免费 | 3篇 |
专业分类
5688篇 |
出版年
2024年 | 3篇 |
2023年 | 24篇 |
2022年 | 52篇 |
2021年 | 101篇 |
2020年 | 65篇 |
2019年 | 51篇 |
2018年 | 77篇 |
2017年 | 69篇 |
2016年 | 124篇 |
2015年 | 234篇 |
2014年 | 273篇 |
2013年 | 347篇 |
2012年 | 429篇 |
2011年 | 435篇 |
2010年 | 281篇 |
2009年 | 265篇 |
2008年 | 332篇 |
2007年 | 353篇 |
2006年 | 353篇 |
2005年 | 345篇 |
2004年 | 305篇 |
2003年 | 338篇 |
2002年 | 297篇 |
2001年 | 46篇 |
2000年 | 31篇 |
1999年 | 54篇 |
1998年 | 72篇 |
1997年 | 43篇 |
1996年 | 43篇 |
1995年 | 33篇 |
1994年 | 34篇 |
1993年 | 29篇 |
1992年 | 26篇 |
1991年 | 21篇 |
1990年 | 14篇 |
1989年 | 12篇 |
1988年 | 5篇 |
1987年 | 9篇 |
1986年 | 11篇 |
1985年 | 9篇 |
1984年 | 8篇 |
1983年 | 3篇 |
1982年 | 5篇 |
1981年 | 4篇 |
1979年 | 5篇 |
1978年 | 6篇 |
1973年 | 4篇 |
1936年 | 1篇 |
1917年 | 1篇 |
1914年 | 1篇 |
排序方式: 共有5688条查询结果,搜索用时 15 毫秒
991.
Christine Decaestecker Xavier Moles Lopez Nicky D'Haene Isabelle Roland Saad Guendouz Christophe Duponchelle Alix Berton Olivier Debeir Isabelle Salmon 《Proteomics》2009,9(19):4478-4494
Antibody‐based proteomics applied to tissue microarray (TMA) technology provides a very efficient means of visualizing and locating antigen expression in large collections of normal and pathological tissue samples. To characterize antigen expression on TMAs, the use of image analysis methods avoids the effects of human subjectivity evidenced in manual microscopical analysis. Thus, these methods have the potential to significantly enhance both precision and reproducibility. Although some commercial systems include tools for the quantitative evaluation of immunohistochemistry‐stained images, there exists no clear agreement on best practices to allow for correct and reproducible quantification results. Our study focuses on practical aspects regarding (i) image acquisition (ii) segmentation of staining and counterstaining areas and (iii) extraction of quantitative features. We illustrate our findings using a commercial system to quantify different immunohistochemistry markers targeting proteins with different expression patterns (cytoplasmic, nuclear or membranous) in colon cancer or brain tumor TMAs. Our investigations led us to identify several steps that we consider essential for standardizing computer‐assisted immunostaining quantification experiments. In addition, we propose a data normalization process based on reference materials to be able to compare measurements between studies involving different TMAs. In conclusion, we recommend certain critical prerequisites that commercial or in‐house systems should satisfy in order to permit valid immunostaining quantification. 相似文献
992.
Nicolò Costantino Brembilla Isabelle Cohen‐Salmon Johann Weber Curzio Rüegg Manfredo Quadroni Keith Harshman Marie‐Agnès Doucey Dr. 《Proteomics》2009,9(2):299-309
The RP protein (RPP) array approach immobilizes minute amounts of cell lysates or tissue protein extracts as distinct microspots on NC‐coated slide. Subsequent detection with specific antibodies allows multiplexed quantification of proteins and their modifications at a scale that is beyond what traditional techniques can achieve. Cellular functions are the result of the coordinated action of signaling proteins assembled in macromolecular complexes. These signaling complexes are highly dynamic structures that change their composition with time and space to adapt to cell environment. Their comprehensive analysis requires until now relatively large amounts of cells (>5×107) due to their low abundance and breakdown during isolation procedure. In this study, we combined small scale affinity capture of the T‐cell receptor (TCR) and RPP arrays to follow TCR signaling complex assembly in human ex vivo isolated CD4 T‐cells. Using this strategy, we report specific recruitment of signaling components to the TCR complex upon T‐cell activation in as few as 0.5 million of cells. Second‐ to fourth‐order TCR interacting proteins were accurately quantified, making this strategy specially well‐suited to the analysis of membrane‐associated signaling complexes in limited amounts of cells or tissues, e.g., ex vivo isolated cells or clinical specimens. 相似文献
993.
Pascal Neige Arnaud Brayard Sylvain Gerber Isabelle Rouget 《Comptes Rendus Palevol》2009,8(2-3):167-178
Ammonoids ruled the seas for 335 Myr and present themselves as an especially suitable model when analyzing biological evolution. This synthetic paper focuses on (1): the phylogenetic place of ammonoids within cephalopods and the choice of an extant reference model; (2): the establishment of phenotypic spaces supplying relevant insights into biological evolution; (3): the concordances and discordances between phylogenetic reconstructions and the fossil record, and (4): the postcrisis recoveries, as models to study large-scale evolution. It appears from these topics that ammonoids can be used as case studies for many themes in Paleontology (biodiversity dynamics, phylogenetics, analysis of the fossil record) that offered and continues to offer a better understanding of evolutionary patterns and processes, especially in the context of large-scale studies. 相似文献
994.
995.
Richard Kraemer Philipp Latzin Isabelle Pramana Pietro Ballinari Sabina Gallati Urs Frey 《Respiratory research》2009,10(1):106
Background and Aim
In patients with cystic fibrosis (CF) the architecture of the developing lungs and the ventilation of lung units are progressively affected, influencing intrapulmonary gas mixing and gas exchange. We examined the long-term course of blood gas measurements in relation to characteristics of lung function and the influence of different CFTR genotype upon this process.Methods
Serial annual measurements of PaO2 and PaCO2 assessed in relation to lung function, providing functional residual capacity (FRCpleth), lung clearance index (LCI), trapped gas (VTG), airway resistance (sReff), and forced expiratory indices (FEV1, FEF50), were collected in 178 children (88 males; 90 females) with CF, over an age range of 5 to 18 years. Linear mixed model analysis and binary logistic regression analysis were used to define predominant lung function parameters influencing oxygenation and carbon dioxide elimination.Results
PaO2 decreased linearly from age 5 to 18 years, and was mainly associated with FRCpleth, (p < 0.0001), FEV1 (p < 0.001), FEF50 (p < 0.002), and LCI (p < 0.002), indicating that oxygenation was associated with the degree of pulmonary hyperinflation, ventilation inhomogeneities and impeded airway function. PaCO2 showed a transitory phase of low PaCO2 values, mainly during the age range of 5 to 12 years. Both PaO2 and PaCO2 presented with different progression slopes within specific CFTR genotypes.Conclusion
In the long-term evaluation of gas exchange characteristics, an association with different lung function patterns was found and was closely related to specific genotypes. Early examination of blood gases may reveal hypocarbia, presumably reflecting compensatory mechanisms to improve oxygenation. 相似文献996.
Eric Jain Amos Bairoch Severine Duvaud Isabelle Phan Nicole Redaschi Baris E Suzek Maria J Martin Peter McGarvey Elisabeth Gasteiger 《BMC bioinformatics》2009,10(1):136-19
Background
The UniProt consortium was formed in 2002 by groups from the Swiss Institute of Bioinformatics (SIB), the European Bioinformatics Institute (EBI) and the Protein Information Resource (PIR) at Georgetown University, and soon afterwards the website was set up as a central entry point to UniProt resources. Requests to this address were redirected to one of the three organisations' websites. While these sites shared a set of static pages with general information about UniProt, their pages for searching and viewing data were different. To provide users with a consistent view and to cut the cost of maintaining three separate sites, the consortium decided to develop a common website for UniProt. Following several years of intense development and a year of public beta testing, the domain was switched to the newly developed site described in this paper in July 2008. 相似文献997.
998.
999.
Laurent Mamelli Sylvain Petit Jacqueline Chevalier Carmela Giglione Aurélie Lieutaud Thierry Meinnel Isabelle Artaud Jean-Marie Pagès 《PloS one》2009,4(7)
Background
Multi-drug resistant (MDR) bacteria have become a major concern in hospitals worldwide and urgently require the development of new antibacterial molecules. Peptide deformylase is an intracellular target now well-recognized for the design of new antibiotics. The bacterial susceptibility to such a cytoplasmic target primarily depends on the capacity of the compound to reach and accumulate in the cytosol.Methodology/Principal Findings
To determine the respective involvement of penetration (influx) and pumping out (efflux) mechanisms to peptide deformylase inhibitors (PDF-I) activity, the potency of various series was determined using various genetic contexts (efflux overproducers or efflux-deleted strains) and membrane permeabilizers. Depending on the structure of the tested molecules, two behaviors could be observed: (i) for actinonin the first PDF-I characterized, the AcrAB efflux system was the main parameter involved in the bacterial susceptibility, and (ii), for the lastest PDF-Is such as the derivatives of 2-(5-bromo-1H-indol-3-yl)-N-hydroxyacetamide, the penetration through the membrane was a important limiting step.Conclusions/Significance
Our results clearly show that the bacterial membrane plays a key role in modulating the antibacterial activity of PDF-Is. The bacterial susceptibility for these new antibacterial molecules can be improved by two unrelated ways in MDR strains: by collapsing the Acr efflux activity or by increasing the uptake rate through the bacterial membrane. The efficiency of the second method is associated with the nature of the compound. 相似文献1000.