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81.
82.
Man-Koumba Soumahoro Patrick Gérardin Pierre-Yves Bo?lle Joelle Perrau Adrian Fianu Jacques Pouchot Denis Malvy Antoine Flahault Fran?ois Favier Thomas Hanslik 《PloS one》2009,4(11)
Background
Persistent symptoms, mainly joint and muscular pain and depression, have been reported several months after Chikungunya virus (CHIKV) infection. Their frequency and their impact on quality of life have not been compared with those of an unexposed population. In the present study, we aimed to describe the frequency of prolonged clinical manifestations of CHIKV infection and to measure the impact on quality of life and health care consumption in comparison with that of an unexposed population, more than one year after infection.Methodology/Principal Findings
In a retrospective cohort study, 199 subjects who had serologically confirmed CHIKV infection (CHIK+) were compared with 199 sero-negative subjects (CHIK–) matched for age, gender and area of residence in La Réunion Island. Following an average time of 17 months from the acute phase of infection, participants were interviewed by telephone about current symptoms, medical consumption during the last 12 months and quality of life assessed by the 12-items Short-Form Health Survey (SF-12) scale. At the time of study, 112 (56%) CHIK+ persons reported they were fully recovered. CHIK+ complained more frequently than CHIK– of arthralgia (relative risk = 1.9; 95% confidence interval: 1.6–2.2), myalgia (1.9; 1.5–2.3), fatigue (2.3; 1.8–3), depression (2.5; 1.5–4.1) and hair loss (3.8; 1.9–7.6). There was no significant difference between CHIK+ and CHIK– subjects regarding medical consumption in the past year. The mean (SD) score of the SF-12 Physical Component Summary was 46.4 (10.8) in CHIK+ versus 49.1 (9.3) in CHIK– (p = 0.04). There was no significant difference between the two groups for the Mental Component Summary.Conclusions/Significance
More than one year following the acute phase of infection, CHIK+ subjects reported more disabilities than those who were CHIK–. These persistent disabilities, however, have no significant influence on medical consumption, and the impact on quality of life is moderate. 相似文献83.
Background
The usual paradigm for translocations is that they should not take place in declining populations until the causes(s) of the decline has been reversed. This approach sounds intuitive, but may not apply in cases where population decline is caused by behavioral or demographic mechanisms that could only be reversed by translocation itself.Methodology/Principal Findings
We analyzed a decade of field data for Pyrenean brown bears (Ursus arctos) from two small populations: the growing Central population - created from a previous translocation and the endemic Western population - believed to be declining because of excessive human-caused mortality. We found that adult survival rates for both populations were as high as those observed for most other protected brown bear populations. However, the Western population had much lower reproductive success than the Central population. Adult breeding sex ratio was male-biased in the Western population and female-biased in the Central population. Our results exclude high anthropogenic mortality as a cause for population decline in the West but support low reproductive success, which could result from sexually selected infanticide induced by a male-biased adult sex ratio or inbreeding depression. Using a stochastic demographic model to compute how many bears should be released to ensure viability, we show that the Western population could recover provided adequate numbers of new females are translocated.Conclusions/Significance
We suggest that a translocation could take place, even if the decline has not yet been reversed, if the translocation itself removes the biological mechanisms behind the decline. In our case, the ultimate cause of low reproductive success remained unknown (infanticide or inbreeding), but our proposed translocation strategies should eliminate the proximate cause (low reproductive success) of the decline and ensure population recovery and viability. 相似文献84.
Elizabeth Faris Crowell Volker Bischoff Thierry Desprez Aurélia Rolland York-Dieter Stierhof Karin Schumacher Martine Gonneau Herman H?fte Samantha Vernhettes 《The Plant cell》2009,21(4):1141-1154
Plant growth and organ formation depend on the oriented deposition of load-bearing cellulose microfibrils in the cell wall. Cellulose is synthesized by plasma membrane–bound complexes containing cellulose synthase proteins (CESAs). Here, we establish a role for the cytoskeleton in intracellular trafficking of cellulose synthase complexes (CSCs) through the in vivo study of the green fluorescent protein (GFP)-CESA3 fusion protein in Arabidopsis thaliana hypocotyls. GFP-CESA3 localizes to the plasma membrane, Golgi apparatus, a compartment identified by the VHA-a1 marker, and, surprisingly, a novel microtubule-associated cellulose synthase compartment (MASC) whose formation and movement depend on the dynamic cortical microtubule array. Osmotic stress or treatment with the cellulose synthesis inhibitor CGA 325''615 induces internalization of CSCs in MASCs, mimicking the intracellular distribution of CSCs in nongrowing cells. Our results indicate that cellulose synthesis is coordinated with growth status and regulated in part through CSC internalization. We find that CSC insertion in the plasma membrane is regulated by pauses of the Golgi apparatus along cortical microtubules. Our data support a model in which cortical microtubules not only guide the trajectories of CSCs in the plasma membrane, but also regulate the insertion and internalization of CSCs, thus allowing dynamic remodeling of CSC secretion during cell expansion and differentiation. 相似文献
85.
Tian L Cai T Pfeffer MA Piankov N Cremieux PY Wei LJ 《Biostatistics (Oxford, England)》2009,10(2):275-281
Recently, meta-analysis has been widely utilized to combine information across comparative clinical studies for evaluating drug efficacy or safety profile. When dealing with rather rare events, a substantial proportion of studies may not have any events of interest. Conventional methods either exclude such studies or add an arbitrary positive value to each cell of the corresponding 2 x 2 tables in the analysis. In this article, we present a simple, effective procedure to make valid inferences about the parameter of interest with all available data without artificial continuity corrections. We then use the procedure to analyze the data from 48 comparative trials involving rosiglitazone with respect to its possible cardiovascular toxicity. 相似文献
86.
87.
Dominique Lesuisse Gilles Tiraboschi Alain Krick Pierre-Yves Abecassis Gilles Dutruc-Rosset Didier Babin Frank Halley Fabienne Châtreau Sylvette Lachaud Alain Chevalier Dominique Quarteronet Marie-Claude Burgevin Céline Amara Philippe Bertrand Thomas Rooney 《Bioorganic & medicinal chemistry letters》2010,20(7):2344-2349
From potent and selective inhibitors of GSK3β displaying CYP1A2 inhibition and poor PK properties, mostly linked to metabolic instability and in vivo hydrolysis of the amide bond, we were able to obtain safe and orally available inhibitors with good half lives. 相似文献
88.
89.
Jean-Philippe Coppé Christopher K. Patil Francis Rodier Ana Krtolica Christian M. Beauséjour Simona Parrinello J. Graeme Hodgson Koei Chin Pierre-Yves Desprez Judith Campisi 《PloS one》2010,5(2)
Cellular senescence irreversibly arrests cell proliferation in response to oncogenic stimuli. Human cells develop a senescence-associated secretory phenotype (SASP), which increases the secretion of cytokines and other factors that alter the behavior of neighboring cells. We show here that “senescent” mouse fibroblasts, which arrested growth after repeated passage under standard culture conditions (20% oxygen), do not express a human-like SASP, and differ from similarly cultured human cells in other respects. However, when cultured in physiological (3%) oxygen and induced to senesce by radiation, mouse cells more closely resemble human cells, including expression of a robust SASP. We describe two new aspects of the human and mouse SASPs. First, cells from both species upregulated the expression and secretion of several matrix metalloproteinases, which comprise a conserved genomic cluster. Second, for both species, the ability to promote the growth of premalignant epithelial cells was due primarily to the conserved SASP factor CXCL-1/KC/GRO-α. Further, mouse fibroblasts made senescent in 3%, but not 20%, oxygen promoted epithelial tumorigenesis in mouse xenographs. Our findings underscore critical mouse-human differences in oxygen sensitivity, identify conditions to use mouse cells to model human cellular senescence, and reveal novel conserved features of the SASP. 相似文献
90.
Dron M Bailly Y Beringue V Haeberlé AM Griffond B Risold PY Tovey MG Laude H Dandoy-Dron F 《Autophagy》2006,2(1):58-60
The Scrg1 gene was initially discovered as one of the genes upregulated in transmissible spongiform encephalopathies (TSE). Scrg1 encodes a highly conserved, cysteine-rich protein expressed principally in the central nervous system. The protein is targeted to the Golgi apparatus and large dense-core vesicles/secretory granules in neurons. We have recently shown that the Scrg1 protein is widely induced in neurons of scrapie-infected mice, suggesting that Scrg1 is involved in the host response to stress and/or the death of neurons. At the ultrastructural level, Scrg1 is associated with dictyosomes of the Golgi apparatus and autophagic vacuoles of degenerative neurons. It is well known that apoptosis plays a major role in the events leading to neuronal cell death in TSE. However, autophagy was identified in experimentally induced scrapie a long time ago and was recently reevaluated as a possible cell death program in prion diseases. The consistent association of Scrg1 with autophagic structures typical of scrapie is in agreement with the recruitment of Golgi-specific proteins in this degradation process and we suggest that Scrg1 might be used as a specific probe to identify neuronal autophagy in TSE. 相似文献