全文获取类型
收费全文 | 2767篇 |
免费 | 220篇 |
国内免费 | 3篇 |
出版年
2023年 | 15篇 |
2022年 | 26篇 |
2021年 | 59篇 |
2020年 | 47篇 |
2019年 | 41篇 |
2018年 | 55篇 |
2017年 | 54篇 |
2016年 | 85篇 |
2015年 | 159篇 |
2014年 | 163篇 |
2013年 | 218篇 |
2012年 | 258篇 |
2011年 | 233篇 |
2010年 | 135篇 |
2009年 | 129篇 |
2008年 | 180篇 |
2007年 | 198篇 |
2006年 | 180篇 |
2005年 | 155篇 |
2004年 | 120篇 |
2003年 | 132篇 |
2002年 | 118篇 |
2001年 | 24篇 |
2000年 | 15篇 |
1999年 | 27篇 |
1998年 | 18篇 |
1997年 | 18篇 |
1996年 | 12篇 |
1995年 | 17篇 |
1994年 | 11篇 |
1993年 | 6篇 |
1992年 | 7篇 |
1991年 | 8篇 |
1990年 | 5篇 |
1989年 | 6篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 5篇 |
1982年 | 3篇 |
1981年 | 4篇 |
1980年 | 4篇 |
1978年 | 2篇 |
1976年 | 5篇 |
1975年 | 4篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1968年 | 2篇 |
排序方式: 共有2990条查询结果,搜索用时 31 毫秒
121.
Infection by pathogens is strongly affected by the diet or condition of the prospective host. Studies that examine the impact of diet have mainly focused on single pathogens; however, co‐infections within a single host are thought to be common. Different pathogen groups might respond differently to resource availability and diverse infections could increase the costs of host defense, meaning the outcome of mixed infections under varying dietary regimes is likely to be hard to predict. We used the generalist cabbage looper, Trichoplusia ni and two of its pathogens, the DNA virus T. ni nucleopolyhedrovirus (TniSNPV) and the entomopathogenic fungus, Beauveria bassiana to examine how nutrient reduction affected the outcome of mixed pathogen infection. We challenged insects with a low or high effective dose of virus, alone or combined with a single dose of fungus. We manipulated food availability after pathogen challenge by diluting artificial diet with cellulose, a non‐nutritious bulking agent, and examined its impact on host and pathogen fitness. Reducing diet quantity did not alter overall or pathogen‐specific mortality. In all cases, TniSNPV‐induced mortality was negatively affected by fungus challenge. Similarly, B. bassiana‐induced mortality was negatively affected by TniSNPV challenge, but only at the higher virus dose. Dietary dilution mainly affected B. bassiana speed of kill when mixed with a high dose of TniSNPV, with an increase in the duration of fungal infection when cellulose was low (high quantity). One pathogen dominated the production of transmission stages in the cadavers and co‐infection did not affect the yield of either pathogen. There was no evidence that co‐infections were more costly to the survivors of pathogen challenge. In conclusion, dietary dilution did not determine the outcome of mixed pathogen infection, but it had more subtle effects, that differed between the two pathogens and could potentially alter pathogen recycling and host–pathogen dynamics. 相似文献
122.
Non-coding variants have long been recognized as important contributors to common disease risks, but with the expansion of clinical whole genome sequencing, examples of rare, high-impact non-coding variants are also accumulating. Despite recent advances in the study of regulatory elements and the availability of specialized data collections, the systematic annotation of non-coding variants from genome sequencing remains challenging. Here, we propose a new framework for the prioritization of non-coding regulatory variants that integrates information about regulatory regions with prediction scores and HPO-based prioritization. Firstly, we created a comprehensive collection of annotations for regulatory regions including a database of 2.4 million regulatory elements (GREEN-DB) annotated with controlled gene(s), tissue(s) and associated phenotype(s) where available. Secondly, we calculated a variation constraint metric and showed that constrained regulatory regions associate with disease-associated genes and essential genes from mouse knock-outs. Thirdly, we compared 19 non-coding impact prediction scores providing suggestions for variant prioritization. Finally, we developed a VCF annotation tool (GREEN-VARAN) that can integrate all these elements to annotate variants for their potential regulatory impact. In our evaluation, we show that GREEN-DB can capture previously published disease-associated non-coding variants as well as identify additional candidate disease genes in trio analyses. 相似文献
123.
124.
Epigenetic control of neural stem cell fate 总被引:18,自引:0,他引:18
125.
Palacio CA García J Arbeláez MP Sánchez R Aguirre B Garcés IC Montoya GJ Gómez J Agudelo A López CA Calle JJ Cardeño CA Cano JF López MC Montoya P Herrera CP González N González A Bedoya G Ruiz A Ospina J 《Biomédica : revista del Instituto Nacional de Salud》2004,24(1):56-62
An interview tool, Diagnostic Interview for Genetic Studies (DIGS 3.0), was translated into Spanish for application in studies of psychiatric disorders in Colombia. Two Spanish translations of the original English version of DIGS were prepared and back-translated into English. A review committee verified the linguistic and cultural equivalence of the translations. The evaluator and test-retest reliability were assessed calculating Cohen's kappa for samples of 65 and 91 patients respectively. DIGS proved valid in both appearance and content. The confidence interval (C.I.) was excellent for schizophrenia (kappa = 0.81, C.I. 95% = 0.68-0.93), bipolar disorder (kappa = 0.87, C.I. 95% = 0.75-0.99), major depressive disorder (kappa = 0.86, C.I. 95% = 0.70-1.00), and for a normal diagnosis (kappa = 0.65, C.I. 95% = 0.41-0.89); it was good for other psychiatric diagnosis (kappa = 0.65, C.I. 95% = 0.41-0.89) and poor for schizoaffective disorder (kappa = 0.37, C.I. 95% = -0.02-0.76). Test-retest reliability was excellent for all diagnoses (kappa > 0.8), except for "other psychiatric diagnoses" (kappa = 0.64, C.I. 95% = 0.31-0.96). The Spanish translation of the DIGS was comprehensible, with face and content validity, and good test-retest and evaluator reliability. This translation will be a useful tool for genetic studies of psychiatric disorders in Latin America, particularly where schizophrenia and affective disorders are involved. 相似文献
126.
The membrane form of the DNA repair protein Ku interacts at the cell surface with metalloproteinase 9 总被引:6,自引:0,他引:6
The Ku heterodimer (Ku70/Ku80) plays a central role in DNA double-strand breaks repair. Ku is also expressed on the cell surface of different types of cells where its function remains poorly understood. From a yeast two-hybrid screen, we have identified a specific interaction between the core region of Ku80 and the hemopexin domain of metalloproteinase 9 (MMP-9), a key enzyme involved in the degradation of extracellular matrix (ECM) components. Ku associates with MMP-9 on the surface of leukemic cells as demonstrated by co-immunoprecipitation experiments in membrane extracts and double-label immunofluorescence studies. In normal and tumoral migratory cells, Ku80 and MMP-9 colocalize at the periphery of leading edge of cells and cellular invasion of collagen IV matrices was blocked by antibodies directed against Ku70 or Ku80 subunits as well as by Ku80-specific antisense oligonucleotides. Our results indicate that Ku and MMP-9 interact at the cell membrane of highly invasive hematopoietic cells of normal and tumoral origin and document the unexpected importance of the membrane-associated form of Ku in the regulation of ECM remodelling. 相似文献
127.
Heasley BH Jarosz R Carter KM Van SJ Lynch KR Macdonald TL 《Bioorganic & medicinal chemistry letters》2004,14(15):4069-4074
A recently reported dual LPA(1)/LPA(3) receptor antagonist (1) has been modified so as to modulate the basicity, sterics, and dipole moment of the 2-pyridyl moiety. Additionally, the implications of installing nonhydrolyzable phosphate head group isosteres with regard to antagonist potency and selectivity at LPA receptors is described. This study has resulted in the development of the first nonhydrolyzable and presumably phosphatase-resistant LPA(3)-selective antagonist reported to date. 相似文献
128.
Cowling JE Weeks JM Spicer JI Gaston KJ 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2004,139(2):251-259
An experimental approach was taken to examine the physiological tolerances that may determine the distribution of the euterrestrial amphipod Arcitalitrus dorrieni, a native of Australia which has established itself in the UK over the last 100 years. Two experiments using mesocosms were carried out over consecutive winters to examine the effects of low temperature and leaf litter sodium content on survival. The role of the microhabitat in buffering environmental temperature was also investigated. It was concluded that A. dorrieni may be prevented from colonising areas of Britain by the effects on populations of low winter temperatures and low habitat sodium concentration. There is considerable buffering of environmental temperatures by the leaf litter and soil layers of the microhabitat, and consequently, mortality of A. dorrieni is related to the depth of microhabitat available for it to utilise in avoiding low temperatures. 相似文献
129.
Kwan Tat S Padrines M Théoleyre S Heymann D Fortun Y 《Cytokine & growth factor reviews》2004,15(1):49-60
All osteogenic cells (osteoclasts, osteoblasts) contribute individually to bone remodeling. Their cellular interactions control their cellular activities and the bone remodeling intensity. These interactions can be established either through a cell-cell contact, involving molecules of the integrin family, or by the release of many polypeptidic factors and/or their soluble receptor chains. These factors can act directly on osteogenic cells and their precursors to control differentiation, formation and functions (matrix formation, mineralization, resorption...). Here, we present the involvement of three groups of cytokines which seem to be of particular importance in bone physiology: interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) (TNF-alpha)/IL-1, and the more recently known triad osteoprotegerin (OPG)/receptor activator of NF-kappaB (RANK)/RANK ligand (RANKL). The interactions between these three groups are presented within the framework of bone resorption pathophysiology such as tumor associated osteolysis. The central role of the OPG/RANK/RANKL triad is pointed out. 相似文献
130.
The GTPase dynamin is essential for numerous vesiculation events including clathrin-mediated endocytosis. Upon GTP hydrolysis, dynamin constricts a lipid bilayer. Previously, a three-dimensional structure of mutant dynamin in the constricted state was determined by helical reconstruction methods. We solved the nonconstricted state by a single-particle approach and show that the stalk region of dynamin undergoes a large conformational change that drives tube constriction. 相似文献