全文获取类型
收费全文 | 2392篇 |
免费 | 186篇 |
出版年
2023年 | 18篇 |
2022年 | 10篇 |
2021年 | 64篇 |
2020年 | 28篇 |
2019年 | 55篇 |
2018年 | 61篇 |
2017年 | 59篇 |
2016年 | 89篇 |
2015年 | 152篇 |
2014年 | 139篇 |
2013年 | 182篇 |
2012年 | 221篇 |
2011年 | 170篇 |
2010年 | 148篇 |
2009年 | 120篇 |
2008年 | 132篇 |
2007年 | 129篇 |
2006年 | 136篇 |
2005年 | 106篇 |
2004年 | 113篇 |
2003年 | 88篇 |
2002年 | 101篇 |
2001年 | 36篇 |
2000年 | 27篇 |
1999年 | 15篇 |
1998年 | 22篇 |
1997年 | 15篇 |
1996年 | 12篇 |
1995年 | 17篇 |
1994年 | 14篇 |
1993年 | 13篇 |
1992年 | 11篇 |
1991年 | 13篇 |
1990年 | 8篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 7篇 |
1986年 | 4篇 |
1985年 | 6篇 |
1984年 | 5篇 |
1983年 | 5篇 |
1982年 | 3篇 |
1980年 | 2篇 |
1977年 | 2篇 |
1971年 | 1篇 |
1969年 | 2篇 |
1962年 | 1篇 |
1959年 | 1篇 |
1957年 | 1篇 |
1952年 | 1篇 |
排序方式: 共有2578条查询结果,搜索用时 20 毫秒
81.
82.
Laura Martin-Fernandez Andrey Ziyatdinov Marina Carrasco Juan Antonio Millon Angel Martinez-Perez Noelia Vilalta Helena Brunel Montserrat Font Anders Hamsten Juan Carlos Souto José Manuel Soria 《PloS one》2016,11(1)
Background
Venous thromboembolism (VTE) is a common disease where known genetic risk factors explain only a small portion of the genetic variance. Then, the analysis of intermediate phenotypes, such as thrombin generation assay, can be used to identify novel genetic risk factors that contribute to VTE.Objectives
To investigate the genetic basis of distinct quantitative phenotypes of thrombin generation and its relationship to the risk of VTE.Patients/Methods
Lag time, thrombin peak and endogenous thrombin potential (ETP) were measured in the families of the Genetic Analysis of Idiopathic Thrombophilia 2 (GAIT-2) Project. This sample consisted of 935 individuals in 35 extended families selected through a proband with idiopathic thrombophilia. We performed also genome wide association studies (GWAS) with thrombin generation phenotypes.Results
The results showed that 67% of the variation in the risk of VTE is attributable to genetic factors. The heritabilities of lag time, thrombin peak and ETP were 49%, 54% and 52%, respectively. More importantly, we demonstrated also the existence of positive genetic correlations between thrombin peak or ETP and the risk of VTE. Moreover, the major genetic determinant of thrombin generation was the F2 gene. However, other suggestive signals were observed.Conclusions
The thrombin generation phenotypes are strongly genetically determined. The thrombin peak and ETP are significantly genetically correlated with the risk of VTE. In addition, F2 was identified as a major determinant of thrombin generation. We reported suggestive signals that might increase our knowledge to explain the variability of this important phenotype. Validation and functional studies are required to confirm GWAS results. 相似文献83.
84.
85.
The macroecology of infectious diseases: a new perspective on global‐scale drivers of pathogen distributions and impacts 下载免费PDF全文
Patrick R. Stephens Sonia Altizer Katherine F. Smith A. Alonso Aguirre James H. Brown Sarah A. Budischak James E. Byers Tad A. Dallas T. Jonathan Davies John M. Drake Vanessa O. Ezenwa Maxwell J. Farrell John L. Gittleman Barbara A. Han Shan Huang Rebecca A. Hutchinson Pieter Johnson Charles L. Nunn David Onstad Andrew Park Gonzalo M. Vazquez‐Prokopec John P. Schmidt Robert Poulin 《Ecology letters》2016,19(9):1159-1171
Identifying drivers of infectious disease patterns and impacts at the broadest scales of organisation is one of the most crucial challenges for modern science, yet answers to many fundamental questions remain elusive. These include what factors commonly facilitate transmission of pathogens to novel host species, what drives variation in immune investment among host species, and more generally what drives global patterns of parasite diversity and distribution? Here we consider how the perspectives and tools of macroecology, a field that investigates patterns and processes at broad spatial, temporal and taxonomic scales, are expanding scientific understanding of global infectious disease ecology. In particular, emerging approaches are providing new insights about scaling properties across all living taxa, and new strategies for mapping pathogen biodiversity and infection risk. Ultimately, macroecology is establishing a framework to more accurately predict global patterns of infectious disease distribution and emergence. 相似文献
86.
A genetic interaction between RAP1 and telomerase reveals an unanticipated role for RAP1 in telomere maintenance 下载免费PDF全文
Paula Martínez Gonzalo Gómez‐López David G. Pisano Juana M. Flores Maria A. Blasco 《Aging cell》2016,15(6):1113-1125
RAP1 is one of the components of shelterin, the capping complex at chromosome ends or telomeres, although its role in telomere length maintenance and protection has remained elusive. RAP1 also binds subtelomeric repeats and along chromosome arms, where it regulates gene expression and has been shown to function in metabolism control. Telomerase is the enzyme that elongates telomeres, and its deficiency causes a premature aging in humans and mice. We describe an unanticipated genetic interaction between RAP1 and telomerase. While RAP1 deficiency alone does not impact on mouse survival, mice lacking both RAP1 and telomerase show a progressively decreased survival with increasing mouse generations compared to telomerase single mutants. Telomere shortening is more pronounced in Rap1?/? Terc?/? doubly deficient mice than in the single‐mutant Terc?/? counterparts, leading to an earlier onset of telomere‐induced DNA damage and degenerative pathologies. Telomerase deficiency abolishes obesity and liver steatohepatitis provoked by RAP1 deficiency. Using genomewide ChIP sequencing, we find that progressive telomere shortening owing to telomerase deficiency leads to re‐localization of RAP1 from telomeres and subtelomeric regions to extratelomeric sites in a genomewide manner. These findings suggest that although in the presence of sufficient telomere reserve RAP1 is not a key factor for telomere maintenance and protection, it plays a crucial role in the context of telomerase deficiency, thus in agreement with its evolutionary conservation as a telomere component from yeast to humans. 相似文献
87.
Einar Vargas-Bello-Pérez Gonzalo Íñiguez-González Nathaly Cancino-Padilla Juan J. Loor Philip C. Garnsworthy 《Archives of animal nutrition》2016,70(4):322-332
The aim of this study was to elucidate the effect of dietary supplementation of soybean oil (SO) and hydrogenated palm oil (HPO) on the transport of fatty acids (FA) within plasma lipoproteins in lactating and non-lactating cows. Three lactating and three non-lactating Holstein cows were used in two different 3 × 3 Latin square experiments that included three periods of 21 d. Dietary treatments for lactating cows consisted of a basal diet (control; no fat supplement) and fat-supplemented diets containing SO (500 g/d per cow) or HPO (500 g/d per cow). For non-lactating cows, dietary treatments consisted of a basal diet (control; no fat supplement) and fat-supplemented diets containing SO (170 g/d per cow) or HPO (170 g/d per cow). Compared with the control and SO diet, HPO addition increased (p < 0.05) the concentration of C16:0, C18:0, C18:2cis-9,12, C18:3cis-9,12,15 and total saturated and polyunsaturated FA in the plasma of lactating cows. In non-lactating cows, the SO addition increased the plasma concentration of C18:1trans-11. In lactating cows, concentrations of C16:0, C18:0 and total saturated FA were increased (p < 0.05) by HPO addition in the high-density lipoprotein (HDL). Total saturated FA were increased (p < 0.05) by HPO in very-low-density lipoprotein (VLDL). In non-lactating cows, the concentration of C18:0 was increased (p < 0.05) by HPO in HDL, whereas C18:1trans-11 was increased (p < 0.05) by SO in the low-density lipoprotein. Overall, it was found that distribution and transport of FA within the bovine plasma lipoproteins may be influenced by chain length and degree of unsaturation of dietary lipids. Also, the distribution of individual FA isomers such as C18:1trans-11 and C18:2cis-9,trans-11 may vary depending on the physiological state of the cow (lactating or non-lactating), and are increased in plasma (lactating cows) and the HDL (non-lactating cows) when cows are fed SO. 相似文献
88.
Montserrat Soler 《Human nature (Hawthorne, N.Y.)》2016,27(4):372-394
Despite secular trends in some countries, prestige-based authority in the form of religious leadership remains hugely influential in the everyday lives of millions of people around the world. Here, the costs and benefits of religious leadership are explored in an urban setting in northeastern Brazil. An economic game, within-group cooperation questionnaires, and social network analyses were carried out among adherents of an Afro-Brazilian religion. Results reveal that leaders display high levels of religious commitment and disproportionally provide cooperative services to group members. On the other hand, initiates cooperate less than leaders but do not differ in levels of received cooperation or social cohesion measures. This may indicate some level of exploitation or free-riding. Demographic and group variables also appear to play an important role in the degree of social cohesion a group achieves. These findings are discussed in the context of non-Western urban settings where religious leadership may represent both an alternative to social advancement and a crucial source of material aid, social support, and a strong sense of community. 相似文献
89.
Maria I. Alvarez‐Mora Petar Podlesniy Ellen Gelpi Renate Hukema Irene Madrigal Javier Pagonabarraga Ramon Trullas Montserrat Mila Laia Rodriguez‐Revenga 《Genes, Brain & Behavior》2019,18(5)
Fragile X‐associated tremor/ataxia syndrome (FXTAS) is a late‐onset neurodegenerative disorder that appears in at least one‐third of adult carriers of a premutation (55‐200 CGG repeats) in the fragile X mental retardation 1 (FMR1) gene. Several studies have shown that mitochondrial dysfunction may play a central role in aging and also in neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease as well as in FXTAS. It has been recently proposed that mtDNA copy number, measured by the number of mitochondrial genomes per nuclear genome (diploid), could be a useful biomarker of mitochondrial dysfunction. In order to elucidate the role of mtDNA variation in the pathogenesis of FXTAS, mtDNA copy number was quantified by digital droplet Polymerase chain reaction. In human brain samples, mtDNA levels were measured in the cerebellar vermis, dentate nucleus, parietal and temporal cortex, thalamus, caudate nucleus and hippocampus from a female FXTAS patient, a FMR1 premutation male carrier without FXTAS and from three male controls. The mtDNA copy number was further analyzed using this technology in dermal fibroblasts primary cultures derived from three FXTAS patients and three controls as well as in cortex and cerebellum of a CGG knock in FXTAS mice model. Finally, qPCR was carried out in human blood samples. Results indicate reduced mtDNA copy number in the specific brain region associated with disease progression in FXTAS patients, providing new insights into the role of mitochondrial dysfunction in the pathogenesis of FXTAS. 相似文献
90.
María N. Barrachina Aurelio M. Sueiro Vanessa Casas Irene Izquierdo Lidia Hermida‐Nogueira Esteban Guitin Felipe F. Casanueva Joaquín Abin Montserrat Carrascal María Pardo ngel García 《Proteomics》2019,19(1-2)
Plasma‐derived extracellular vesicles (EVs) have been extensively described as putative biomarkers in different diseases. Interestingly, increased levels of EVs subpopulations are well known to associate with obesity. The goal of this study is to identify EVs‐derived biomarkers in plasma from obese patients in order to predict the development of pathological events associated with obesity. Samples are obtained from 22 obese patients and their lean‐matched controls are divided into two cohorts: one for a 2D fluorescence difference gel electrophoresis (2D‐DIGE)‐based study, and the other one for a label free LC–MS/MS‐based approach. EVs are isolated following a serial ultracentrifugation protocol. Twenty‐two and 23 differentially regulated features are detected from 2D‐DIGE and label free LC–MS/MS, respectively; most of them involve in the coagulation and complement cascades. Remarkably, there is an upregulation of complement C4, complement C3, and fibrinogen in obese patients following both approaches, the latter two also validated by 2D‐western‐blotting in an independent cohort. These results correlate with a proinflammatory and prothrombotic state of those individuals. On the other hand, a downregulation of adiponectin leading to an increased risk of suffering cardiovascular diseases has been shown. The results suggest the relevance of plasma‐derived‐EVs proteins as a source of potential biomarkers for the development of atherothrombotic events in obesity. 相似文献