全文获取类型
收费全文 | 523篇 |
免费 | 43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.
472.
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473.
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
474.
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
475.
The hierarchy of the segmentation cascade responsible for establishing the Drosophila body plan is composed by gap, pair-rule and segment polarity genes. However, no pair-rule stripes are formed in the anterior regions of the embryo. This lack of stripe formation, as well as other evidence from the literature that is further investigated here, led us to the hypothesis that anterior gap genes might be involved in a combinatorial mechanism responsible for repressing the cis-regulatory modules (CRMs) of hairy (h), even-skipped (eve), runt (run), and fushi-tarazu (ftz) anterior-most stripes. In this study, we investigated huckebein (hkb), which has a gap expression domain at the anterior tip of the embryo. Using genetic methods we were able to detect deviations from the wild-type patterns of the anterior-most pair-rule stripes in different genetic backgrounds, which were consistent with Hkb-mediated repression. Moreover, we developed an image processing tool that, for the most part, confirmed our assumptions. Using an hkb misexpression system, we further detected specific repression on anterior stripes. Furthermore, bioinformatics analysis predicted an increased significance of binding site clusters in the CRMs of h 1, eve 1, run 1 and ftz 1when Hkb was incorporated in the analysis, indicating that Hkb plays a direct role in these CRMs. We further discuss that Hkb and Slp1, which is the other previously identified common repressor of anterior stripes, might participate in a combinatorial repression mechanism controlling stripe CRMs in the anterior parts of the embryo and define the borders of these anterior stripes. 相似文献
476.
477.
Carla A. Maissen-Villiger Ariane Schweighauser H. Anette van Dorland Claudine Morel Rupert M. Bruckmaier Andreas Zurbriggen Thierry Francey 《PloS one》2016,11(1)
Background
Dogs with leptospirosis show similar organ manifestations and disease course as human patients, including acute kidney injury and pulmonary hemorrhage, making this naturally-occurring infection a good animal model for human leptospirosis. Expression patterns of cytokines and enzymes have been correlated with disease manifestations and clinical outcome in humans and animals. The aim of this study was to describe mRNA expression of pro- and anti-inflammatory mediators in canine leptospirosis and to compare it with other renal diseases to identify patterns characterizing the disease and especially its pulmonary form.Methodology and Principal Findings
The mRNA abundance of cytokines (IL-1α, IL-1β, IL-8, IL-10, TNF-α, TGF-β) and enzymes (5-LO, iNOS) was measured prospectively in blood leukocytes from 34 dogs with severe leptospirosis and acute kidney injury, including 22 dogs with leptospirosis-associated pulmonary hemorrhages. Dogs with leptospirosis were compared to 14 dogs with acute kidney injury of other origin than leptospirosis, 8 dogs with chronic kidney disease, and 10 healthy control dogs. Canine leptospirosis was characterized by high 5-LO and low TNF-α expression compared to other causes of acute kidney injury, although the decreased TNF-α expression was also seen in chronic kidney disease. Leptospirosis-associated pulmonary hemorrhage was not characterized by a specific pattern, with only mild changes noted, including increased IL-10 and decreased 5-LO expression on some days in affected dogs. Fatal outcome from pulmonary hemorrhages was associated with low TNF-α, high IL-1β, and high iNOS expression, a pattern possibly expressed also in dogs with other forms of acute kidney injury.Conclusion
The patterns of cytokine and enzyme expression observed in the present study indicate a complex pro- and anti-inflammatory response to the infection with leptospires. The recognition of these signatures may be of diagnostic and prognostic relevance for affected individuals and they may indicate options for newer therapies targeting the identified pathways. 相似文献478.
Prevention and treatment of enteric viral infections: possible benefits of probiotic bacteria 总被引:1,自引:0,他引:1
Colbère-Garapin F Martin-Latil S Blondel B Mousson L Pelletier I Autret A François A Niborski V Grompone G Catonnet G van de Moer A 《Microbes and infection / Institut Pasteur》2007,9(14-15):1623-1631
The structure and function of the intestinal epithelium is briefly described, with the principal mechanisms involved in diarrhea. Human enteric viruses and probiotics are presented. We then review how probiotic bacteria could interfere with virus-induced pathology, we present our own view and describe specific interactions that would be valuable targets for future studies. 相似文献
479.
Krasinska L de Bettignies G Fisher D Abrieu A Fesquet D Morin N 《Experimental cell research》2007,313(6):1225-1239
Whereas early cytokinesis events have been relatively well studied, little is known about its final stage, abscission. The Cdc14 phosphatase is involved in the regulation of multiple cell cycle events, and in all systems studied Cdc14 misexpression leads to cytokinesis defects. In this work, we have cloned two CDC14 cDNA from Xenopus, including a previously unreported CDC14B homologue. We use Xenopus and human cell lines and demonstrate that localization of Cdc14 proteins is independent of both cell-type and species specificity. Ectopically expressed XCdc14A is centrosomal in interphase and localizes to the midbody in cytokinesis. By using XCdc14A misregulation, we confirm its control over different cell cycle events and unravel new functions during abscission. XCdc14A regulates the G1/S and G2/M transitions. We show that Cdc25 is an in vitro substrate for XCdc14A and might be its target at the G2/M transition. Upregulated wild-type or phosphatase-dead XCdc14A arrest cells in a late stage of cytokinesis, connected by thin cytoplasmic bridges. It does not interfere with central spindle formation, nor with the relocalization of passenger protein and centralspindlin complexes to the midbody. We demonstrate that XCdc14A upregulation prevents targeting of exocyst and SNARE complexes to the midbody, both essential for abscission to occur. 相似文献
480.