全文获取类型
收费全文 | 523篇 |
免费 | 43篇 |
专业分类
566篇 |
出版年
2023年 | 4篇 |
2022年 | 10篇 |
2021年 | 12篇 |
2020年 | 9篇 |
2019年 | 15篇 |
2018年 | 11篇 |
2017年 | 21篇 |
2016年 | 23篇 |
2015年 | 23篇 |
2014年 | 26篇 |
2013年 | 37篇 |
2012年 | 45篇 |
2011年 | 55篇 |
2010年 | 28篇 |
2009年 | 23篇 |
2008年 | 36篇 |
2007年 | 24篇 |
2006年 | 26篇 |
2005年 | 23篇 |
2004年 | 14篇 |
2003年 | 26篇 |
2002年 | 18篇 |
2001年 | 4篇 |
2000年 | 5篇 |
1999年 | 1篇 |
1998年 | 5篇 |
1997年 | 4篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 4篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1989年 | 2篇 |
1986年 | 1篇 |
1985年 | 4篇 |
1984年 | 1篇 |
1982年 | 2篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 4篇 |
1976年 | 1篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1969年 | 3篇 |
排序方式: 共有566条查询结果,搜索用时 15 毫秒
471.
Giacoia-Gripp CB Sales AM Nery JA Santos-Oliveira JR de Oliveira AL Sarno EN Morgado MG 《PloS one》2011,6(12):e28735
Background
It is now evident that HAART-associated immunological improvement often leads to a variety of new clinical manifestations, collectively termed immune reconstitution inflammatory syndrome, or IRIS. This phenomenon has already been described in cases of HIV coinfection with Mycobacterium leprae, most of them belonging to the tuberculoid spectrum of leprosy disease, as observed in leprosy reversal reaction (RR). However, the events related to the pathogenesis of this association need to be clarified. This study investigated the immunological profile of HIV/leprosy patients, with special attention to the cellular activation status, to better understand the mechanisms related to IRIS/RR immunopathogenesis, identifying any potential biomarkers for IRIS/RR intercurrence.Methods/Principal Findings
Eighty-five individuals were assessed in this study: HIV/leprosy and HIV-monoinfected patients, grouped according to HIV-viral load levels, leprosy patients without HIV coinfection, and healthy controls. Phenotypes were evaluated by flow cytometry for T cell subsets and immune differentiation/activation markers. As expected, absolute counts of the CD4+ and CD8+ T cells from the HIV-infected individuals changed in relation to those of the leprosy patients and controls. However, there were no significant differences among the groups, whether in the expression of cellular differentiation phenotypes or cellular activation, as reflected by the expression of CD38 and HLA-DR. Six HIV/leprosy patients identified as IRIS/RR were analyzed during IRIS/RR episodes and after prednisone treatment. These patients presented high cellular activation levels regarding the expression of CD38 in CD8+ cells T during IRIS/RR (median: 77,15%), dropping significantly (p<0,05) during post-IRIS/RR moments (median: 29,7%). Furthermore, an increase of cellular activation seems to occur prior to IRIS/RR.Conclusion/Significance
These data suggest CD38 expression in CD8+ T cells interesting tool identifying HIV/leprosy individuals at risk for IRIS/RR. So, a comparative investigation to leprosy patients at RR should be conducted. 相似文献472.
Although, most studies of human skeletal muscle in vivo have reported the co-existence of impaired insulin sensitivity and reduced expression of oxidative phosphorylation genes, there is so far no clear evidence for whether the intrinsic ATP synthesis is primarily decreased or not in the mitochondria of diabetic skeletal muscle from subjects with type 2 diabetes. ATP synthesis was measured on mitochondria isolated from cultured myotubes established from lean (11/9), obese (9/11) and subjects with type 2 diabetes (9/11) (female/male, n = 20 in each group), precultured under normophysiological conditions in order to verify intrinsic impairments. To resemble dynamic equilibrium present in whole cells between ATP synthesis and utilization, ATP was measured in the presence of an ATP consuming enzyme, hexokinase, under steady state. Mitochondria were isolated using an affinity based method which selects the mitochondria based on an antibody recognizing the mitochondrial outer membrane and not by size through gradient centrifugation. The dynamic equilibrium between ATP synthesis and ATP consumption is 35% lower in isolated mitochondria from myotubes established from type 2 diabetic subjects compared to lean control. The ATP synthesis rate without ATP consumption was not different between groups and there were no significant gender differences. The mitochondrial dysfunction in type 2 diabetes in vivo is partly based on a primarily impaired ATP synthesis. 相似文献
473.
474.
475.
476.
B?umler W Regensburger J Knak A Felgentr?ger A Maisch T 《Photochemical & photobiological sciences》2012,11(1):107-117
UVA irradiation (320-400 nm) comprises about 95 percent of incident midday solar ultraviolet irradiation. It penetrates skin much deeper than UVB irradiation. The absorption of UVA irradiation in endogenous chromophores frequently leads to the generation of reactive oxygen species such as singlet oxygen ((1)O(2)). (1)O(2) is an important biochemical intermediate in multiple biological processes. Beside other procedures, the direct detection of (1)O(2) by its luminescence is a powerful tool that helps to understand the generation of (1)O(2) during UVA exposure in solution, in vitro and in vivo. This article describes the endogenous photosensitizers, their ability to generate (1)O(2) under UVA irradiation, and the detection technology to visualize the action of (1)O(2). 相似文献
477.
478.
Lara Bossini-Castillo Carmen P Simeon Lorenzo Beretta Jasper Broen Madelon C Vonk José Luis Callejas Patricia Carreira Luis Rodríguez-Rodríguez Rosa García-Portales Miguel A González-Gay Ivan Castellví María Teresa Camps Carlos Tolosa Esther Vicente-Rabaneda María Victoria Egurbide Annemie J Schuerwegh Roger Hesselstrand Claudio Lunardi Jacob M van Laar Paul Shiels Ariane Herrick Jane Worthington Christopher Denton Timothy RDJ Radstake Carmen Fonseca Javier Martin 《Arthritis research & therapy》2012,14(6):R273
Introduction
Potassium voltage-gated channel shaker-related subfamily member 5 (KCNA5) is implicated in vascular tone regulation, and its inhibition during hypoxia produces pulmonary vasoconstriction. Recently, a protective association of the KCNA5 locus with systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) was reported. Hence, the aim of this study was to replicate these findings in an independent multicenter Caucasian SSc cohort.Methods
The 2,343 SSc cases (179 PAH positive, confirmed by right-heart catheterization) and 2,690 matched healthy controls from five European countries were included in this study. Rs10744676 single-nucleotide polymorphism (SNP) was genotyped by using a TaqMan SNP genotyping assay.Results
Individual population analyses of the selected KCNA5 genetic variant did not show significant association with SSc or any of the defined subsets (for example, limited cutaneous SSc, diffuse cutaneous SSc, anti-centromere autoantibody positive and anti-topoisomerase autoantibody positive). Furthermore, pooled analyses revealed no significant evidence of association with the disease or any of the subsets, not even the PAH-positive group. The comparison of PAH-positive patients with PAH-negative patients showed no significant differences among patients.Conclusions
Our data do not support an important role of KCNA5 as an SSc-susceptibility factor or as a PAH-development genetic marker for SSc patients. 相似文献479.
Lara Bossini-Castillo Carmen P Simeon Lorenzo Beretta Jasper C Broen Madelon C Vonk Raquel Ríos-Fernández Gerard Espinosa Patricia Carreira María T Camps Maria J Castillo Miguel A González-Gay Emma Beltrán María del Carmen Freire Javier Narváez Carlos Tolosa Torsten Witte Alexander Kreuter Annemie J Schuerwegh Anna-Maria Hoffmann-Vold Roger Hesselstrand Claudio Lunardi Jacob M van Laar Meng May Chee Ariane Herrick Bobby PC Koeleman Christopher P Denton Carmen Fonseca Timothy RDJ Radstake Javier Martin 《Arthritis research & therapy》2012,14(2):1-7
Idiopathic inflammatory myopathies (IIMs) comprise a group of autoimmune diseases that are characterized by symmetrical skeletal muscle weakness and muscle inflammation with no known cause. Like other autoimmune diseases, IIMs are treated with either glucocorticoids or immunosuppressive drugs. However, many patients with an IIM are frequently resistant to immunosuppressive treatments, and there is compelling evidence to indicate that not only adaptive immune but also several non-immune mechanisms play a role in the pathogenesis of these disorders. Here, we focus on some of the evidence related to pathologic mechanisms, such as the innate immune response, endoplasmic reticulum stress, non-immune consequences of MHC class I overexpression, metabolic disturbances, and hypoxia. These mechanisms may explain how IIM-related pathologic processes can continue even in the face of immunosuppressive therapies. These data indicate that therapeutic strategies in IIMs should be directed at both immune and non-immune mechanisms of muscle damage. 相似文献
480.
Four new species of Ixora (Rubiaceae, Ixoreae) from Brazil are described and illustrated and their relationships to morphologically similar species as well as their conservation status are discussed. The new species, Ixora cabraliensis, Ixora emygdioi, Ixora grazielae, and Ixora pilosostyla are endemic to the Atlantic Forest of southern Bahia and Espirito Santo. 相似文献