全文获取类型
收费全文 | 5209篇 |
免费 | 459篇 |
国内免费 | 3篇 |
专业分类
5671篇 |
出版年
2024年 | 3篇 |
2023年 | 24篇 |
2022年 | 52篇 |
2021年 | 100篇 |
2020年 | 65篇 |
2019年 | 51篇 |
2018年 | 77篇 |
2017年 | 67篇 |
2016年 | 124篇 |
2015年 | 234篇 |
2014年 | 272篇 |
2013年 | 346篇 |
2012年 | 426篇 |
2011年 | 430篇 |
2010年 | 281篇 |
2009年 | 265篇 |
2008年 | 331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 | 71篇 |
1997年 | 44篇 |
1996年 | 43篇 |
1995年 | 32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 |
1972年 | 1篇 |
1966年 | 1篇 |
1936年 | 1篇 |
排序方式: 共有5671条查询结果,搜索用时 15 毫秒
991.
Déborah Ducasse Isabelle Jaussent Emilie Olié Sébastien Guillaume Jorge Lopez-Castroman Philippe Courtet 《PloS one》2016,11(2)
Objective
Both Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD) might increase the risk of suicidal behavior. The aim of this study was to assess the relationship between personality dimensions specifically involved in suicidal vulnerability and PMS/PMDD.Method
We collected data from 232 women consecutively hospitalized after a suicide attempt. We examined the relationship between impulsivity, aggressiveness/hostility, hopelessness, trait anger, affect intensity, emotional lability, and PMS/PMDD. Notably, we created an algorithm from the shortened Premenstrual Assessment form in order to assess PMDD status.Results
The proportions of PMS and PMDD among female suicide attempters were 50% and 23% respectively. Women with PMS or PMDD were more likely to endorse most of these personality traits to than those without even after controlling for potential confounders. We found an impulsive-aggressive pattern of personality in women with PMS or PMDD, independently from the time of the menstrual cycle. Interestingly, trait anger remained associated with both PMS and PMDD independently of every other personality traits. The higher the anger level, the higher the risk was to suffer from both PMS and PMDD.Conclusions
This study demonstrates a strong, independent association between PMS/PMDD and trait anger among a representative sample of female suicide attempters. It is of major interest for clinicians in view of addressing a substantial public health problem among women of reproductive age. 相似文献992.
Andreea Mihaela Seferian Amélie Moraux Mélanie Annoussamy Aurélie Canal Valérie Decostre Oumar Diebate Anne-Ga?lle Le Moing Teresa Gidaro Nicolas Deconinck Frauke Van Parys Wendy Vereecke Sylvia Wittevrongel Michèle Mayer Kim Maincent Isabelle Desguerre Christine Thémar-No?l Jean-Marie Cuisset Vincent Tiffreau Severine Denis Virginie Jousten Susana Quijano-Roy Thomas Voit Jean-Yves Hogrel Laurent Servais 《PloS one》2015,10(2)
IntroductionUpper limb evaluation of patients with Duchenne Muscular Dystrophy is crucially important to evaluations of efficacy of new treatments in non-ambulant patients. In patients who have lost ambulation, there are few validated and informative outcome measures. In addition, longitudinal data demonstrating sensitivity to clinical evolution of outcome measures over short-term periods are lacking.ResultsOur study confirmed preliminary data previously reported regarding feasibility of use and of reliability of the MyoSet and the correlation at baseline between distal strength and clinical outcomes such as FVC, Brooke score, age, and duration since loss of ambulation. A significant correlation was observed between the distal upper limb strength and clinical variables. The sensitive dynamometers (MyoGrip and MyoPinch) and MoviPlate captured a 12-month change in non-ambulant Duchenne muscular dystrophy patients of all ages.
Trial Registration
ClinicalTrials.gov NCT00993161 NCT00993161相似文献993.
Arancha Catalan-Moreno Marta Cela Pilar Menendez-Gil Naiara Irurzun Carlos
J Caballero Isabelle Caldelari Alejandro Toledo-Arana 《Nucleic acids research》2021,49(6):3409
Thermoregulation of virulence genes in bacterial pathogens is essential for environment-to-host transition. However, the mechanisms governing cold adaptation when outside the host remain poorly understood. Here, we found that the production of cold shock proteins CspB and CspC from Staphylococcus aureus is controlled by two paralogous RNA thermoswitches. Through in silico prediction, enzymatic probing and site-directed mutagenesis, we demonstrated that cspB and cspC 5′UTRs adopt alternative RNA structures that shift from one another upon temperature shifts. The open (O) conformation that facilitates mRNA translation is favoured at ambient temperatures (22°C). Conversely, the alternative locked (L) conformation, where the ribosome binding site (RBS) is sequestered in a double-stranded RNA structure, is folded at host-related temperatures (37°C). These structural rearrangements depend on a long RNA hairpin found in the O conformation that sequesters the anti-RBS sequence. Notably, the remaining S. aureus CSP, CspA, may interact with a UUUGUUU motif located in the loop of this long hairpin and favour the folding of the L conformation. This folding represses CspB and CspC production at 37°C. Simultaneous deletion of the cspB/cspC genes or their RNA thermoswitches significantly decreases S. aureus growth rate at ambient temperatures, highlighting the importance of CspB/CspC thermoregulation when S. aureus transitions from the host to the environment. 相似文献
994.
Sturchler E Cox JA Durussel I Weibel M Heizmann CW 《The Journal of biological chemistry》2006,281(50):38905-38917
S100A16 protein is a new and unique member of the EF-hand Ca(2+)-binding proteins. S100 proteins are cell- and tissue-specific and are involved in many intra- and extracellular processes through interacting with specific target proteins. In the central nervous system S100 proteins are implicated in cell proliferation, differentiation, migration, and apoptosis as well as in cognition. S100 proteins became of major interest because of their close association with brain pathologies, for example depression or Alzheimer's disease. Here we report for the first time the purification and biochemical characterization of human and mouse recombinant S100A16 proteins. Flow dialysis revealed that both homodimeric S100A16 proteins bind two Ca(2+) ions with the C-terminal EF-hand of each subunit, the human protein exhibiting a 2-fold higher affinity. Trp fluorescence variations indicate conformational changes in the orthologous proteins upon Ca(2+) binding, whereas formation of a hydrophobic patch, implicated in target protein recognition, only occurs in the human S100A16 protein. In situ hybridization analysis and immunohistochemistry revealed a widespread distribution in the mouse brain. Furthermore, S100A16 expression was found to be astrocyte-specific. Finally, we investigated S100A16 intracellular localization in human glioblastoma cells. The protein was found to accumulate within nucleoli and to translocate to the cytoplasm in response to Ca(2+) stimulation. 相似文献
995.
de Batlle J Sauleda J Balcells E Gómez FP Méndez M Rodriguez E Barreiro E Ferrer JJ Romieu I Gea J Antó JM Garcia-Aymerich J;PAC-COPD Study Group 《The Journal of nutritional biochemistry》2012,23(7):817-821
Dietary intake of polyunsaturated fatty acids, including omega-3 and omega-6, could modulate chronic obstructive pulmonary disease (COPD) persistent inflammation. We aimed to assess the relationship between dietary intake of omega-3 and omega-6 fatty acids and serum inflammatory markers in COPD. A total of 250 clinically stable COPD patients were included. Dietary data of the last 2 years were assessed using a validated food frequency questionnaire (122 items), which provided levels of three omega-3 fatty acids: docosahexaenoic acid, eicosapentaenoic acid and α-linolenic acid (ALA); and two omega-6 fatty acids: linoleic acid and arachidonic acid (AA). Inflammatory markers [C-reactive protein (CRP), interleukin (IL)-6, IL-8 and tumor necrosis factor alpha (TNFα)] were measured in serum. Fatty acids and inflammatory markers were dichotomised according to their median values, and their association was assessed using multivariate logistic regression. Higher intake of ALA (an anti-inflammatory omega-3 fatty acid) was associated with lower TNFα concentrations [adjusted odds ratio (OR)=0.46; P=.049]. Higher AA intake (a proinflammatory omega-6 fatty acid) was related to higher IL-6 (OR=1.96; P=.034) and CRP (OR=1.95; P=.039) concentrations. Therefore, this study provides the first evidence of an association between dietary intake of omega-3 and omega-6 fatty acids and serum inflammatory markers in COPD patients. 相似文献
996.
Host cell invasion by Toxoplasma gondii tachyzoites relies on many coordinated processes. The tachyzoite participates in invasion by providing an actomyosin-dependent force driving it into the nascent parasitophorous vacuole as well as by releasing molecules which contribute to the vacuole membrane. Exposure to type 1/2A protein phosphatase inhibitors, okadaic acid (OA) or tautomycin significantly impairs tachyzoite invasiveness. Furthermore, the tachyzoite extract contains a biochemically active type 1, but not a type 2A, serine-threonine protein phosphatase, which is immunologically related to eukaryotic phosphatase type 1 catalytic subunit. When tachyzoite extracts are incubated with a monoclonal antibody reactive to human type 1 catalytic subunit, other T. gondii molecules are coprecipitated among which one competes with the inhibitory toxin OA. Finally, in vitro phosphate labelling assays indicate that the biochemically characterized PP1 activity controls the phosphorylation of several proteins. Taken together, these data strongly suggest that the type 1 phosphatase activity detected in invasive tachyzoites is implicated in the control of the host cell invasion process. 相似文献
997.
Cellular aging is characterized by the build-up of oxidatively modified protein that results, at least in part, from impaired redox homeostasis associated with the aging process. Protein degradation and repair are critical for eliminating oxidized proteins from the cell. Oxidized protein degradation is mainly achieved by the proteasomal system and it is now well established that proteasomal function is generally impaired with age. Specific enzymatic systems have been identified which catalyze the regeneration of cysteine and methionine following oxidation within proteins. Protein-bound methionine sulfoxide diastereoisomers S and R are repaired by the combined action of the enzymes MsrA and MsrB that are subsequently regenerated by thioredoxin/thioredoxin reductase. Importantly, the peptide methionine sulfoxide reductase system has been implicated in increased longevity and resistance to oxidative stress in different cell types and model organisms. In a previous study, we reported that peptide methionine sulfoxide reductase activity as well as gene and protein expression of MsrA are decreased in various organs as a function of age. More recently, we have shown that gene expression of both MsrA and MsrB2 (Cbs-1) is decreased during replicative senescence of WI-38 fibroblasts, and this decline is associated with an alteration in catalytic activity and the accumulation of oxidized protein. In this review, we will address the importance of protein maintenance in the aging process as well as in replicative senescence, with a special focus on regulation of the peptide methionine sulfoxide reductase systems. 相似文献
998.
Social and spatial effects on genetic variation between foraging flocks in a wild bird population 下载免费PDF全文
Reinder Radersma Colin J. Garroway Anna W. Santure Isabelle de Cauwer Damien R. Farine Jon Slate Ben C. Sheldon 《Molecular ecology》2017,26(20):5807-5819
Social interactions are rarely random. In some instances, animals exhibit homophily or heterophily, the tendency to interact with similar or dissimilar conspecifics, respectively. Genetic homophily and heterophily influence the evolutionary dynamics of populations, because they potentially affect sexual and social selection. Here, we investigate the link between social interactions and allele frequencies in foraging flocks of great tits (Parus major) over three consecutive years. We constructed co‐occurrence networks which explicitly described the splitting and merging of 85,602 flocks through time (fission–fusion dynamics), at 60 feeding sites. Of the 1,711 birds in those flocks, we genotyped 962 individuals at 4,701 autosomal single nucleotide polymorphisms (SNPs). By combining genomewide genotyping with repeated field observations of the same individuals, we were able to investigate links between social structure and allele frequencies at a much finer scale than was previously possible. We explicitly accounted for potential spatial effects underlying genetic structure at the population level. We modelled social structure and spatial configuration of great tit fission–fusion dynamics with eigenvector maps. Variance partitioning revealed that allele frequencies were strongly affected by group fidelity (explaining 27%–45% of variance) as individuals tended to maintain associations with the same conspecifics. These conspecifics were genetically more dissimilar than expected, shown by genomewide heterophily for pure social (i.e., space‐independent) grouping preferences. Genomewide homophily was linked to spatial configuration, indicating spatial segregation of genotypes. We did not find evidence for homophily or heterophily for putative socially relevant candidate genes or any other SNP markers. Together, these results demonstrate the importance of distinguishing social and spatial processes in determining population structure. 相似文献
999.
William J. Sutherland Phoebe Barnard Steven Broad Mick Clout Ben Connor Isabelle M. Côté Lynn V. Dicks Helen Doran Abigail C. Entwistle Erica Fleishman Marie Fox Kevin J. Gaston David W. Gibbons Zhigang Jiang Brandon Keim Fiona A. Lickorish Paul Markillie Kathryn A. Monk Nancy Ockendon 《Trends in ecology & evolution》2017,32(1):31-40
1000.
Obeticholic acid improves adipose morphometry and inflammation and reduces steatosis in dietary but not metabolic obesity in mice 下载免费PDF全文