全文获取类型
收费全文 | 305篇 |
免费 | 30篇 |
出版年
2023年 | 3篇 |
2022年 | 5篇 |
2021年 | 5篇 |
2020年 | 4篇 |
2019年 | 4篇 |
2018年 | 4篇 |
2017年 | 7篇 |
2016年 | 7篇 |
2015年 | 11篇 |
2014年 | 12篇 |
2013年 | 11篇 |
2012年 | 13篇 |
2011年 | 11篇 |
2010年 | 8篇 |
2009年 | 8篇 |
2008年 | 16篇 |
2007年 | 11篇 |
2006年 | 8篇 |
2005年 | 16篇 |
2004年 | 14篇 |
2003年 | 6篇 |
2002年 | 12篇 |
2001年 | 15篇 |
2000年 | 7篇 |
1999年 | 9篇 |
1998年 | 10篇 |
1997年 | 5篇 |
1996年 | 5篇 |
1995年 | 7篇 |
1994年 | 2篇 |
1993年 | 4篇 |
1992年 | 9篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1986年 | 3篇 |
1984年 | 3篇 |
1981年 | 2篇 |
1977年 | 6篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1970年 | 2篇 |
1969年 | 2篇 |
1966年 | 2篇 |
1963年 | 4篇 |
1918年 | 2篇 |
1912年 | 1篇 |
1911年 | 2篇 |
排序方式: 共有335条查询结果,搜索用时 312 毫秒
71.
72.
73.
74.
75.
Impaired neutrophil extracellular trap formation: a novel defect in the innate immune system of aged individuals 总被引:1,自引:0,他引:1
Jon Hazeldine Phillipa Harris Iain L. Chapple Melissa Grant Hannah Greenwood Amy Livesey Elizabeth Sapey Janet M. Lord 《Aging cell》2014,13(4):690-698
Neutrophil extracellular traps (NETs) are a recently discovered addition to the defensive armamentarium of neutrophils, assisting in the immune response against rapidly dividing bacteria. Although older adults are more susceptible to such infections, no study has examined whether aging in humans influences NET formation. We report that TNF‐α‐primed neutrophils generate significantly more NETs than unprimed neutrophils and that lipopolysaccharide (LPS)‐ and interleukin‐8 (IL‐8)‐induced NET formation exhibits a significant age‐related decline. NET formation requires generation of reactive oxygen species (ROS), and this was also reduced in neutrophils from older donors identifying a mechanism for reduced NET formation. Expression of IL‐8 receptors (CXCR1 and CXCR2) and the LPS receptor TLR4 was similar on neutrophils from young and old subjects, and neutrophils challenged with phorbol‐12‐myristate‐13‐acetate (PMA) showed no age‐associated differences in ROS or NET production. Taken together, these data suggest a defect in proximal signalling underlies the age‐related decline in NET and ROS generation. TNF‐α priming involves signalling through p38 MAP kinase, but activation kinetics were comparable in neutrophils from young and old donors. In a clinical setting, we assessed the capacity of neutrophils from young and older patients with chronic periodontitis to generate NETs in response to PMA and hypochlorous acid (HOCL). Neutrophil extracellular trap generation to HOCL, but not PMA, was lower in older periodontitis patients but not in comparison with age‐matched controls. Impaired NET formation is thus a novel defect of innate immunity in older adults but does not appear to contribute to the increased incidence of periodontitis in older adults. 相似文献
76.
A cDNA encoding a novel cytochrome P450-dependent monooxygenase from Arabidopsis thaliana. 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Plant physiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
C C Chapple 《Plant physiology》1995,108(2):875-876
77.
78.
79.
80.
Nicoll WS Botha M McNamara C Schlange M Pesce ER Boshoff A Ludewig MH Zimmermann R Cheetham ME Chapple JP Blatch GL 《The international journal of biochemistry & cell biology》2007,39(4):736-751
Both prokaryotic and eukaryotic cells contain multiple heat shock protein 40 (Hsp40) and heat shock protein 70 (Hsp70) proteins, which cooperate as molecular chaperones to ensure fidelity at all stages of protein biogenesis. The Hsp40 signature domain, the J-domain, is required for binding of an Hsp40 to a partner Hsp70, and may also play a role in the specificity of the association. Through the creation of chimeric Hsp40 proteins by the replacement of the J-domain of a prokaryotic Hsp40 (DnaJ), we have tested the functional equivalence of J-domains from a number of divergent Hsp40s of mammalian and parasitic origin (malarial Pfj1 and Pfj4, trypanosomal Tcj3, human ERj3, ERj5, and Hsj1, and murine ERj1). An in vivo functional assay was used to test the functionality of the chimeric proteins on the basis of their ability to reverse the thermosensitivity of a dnaJ cbpA mutant Escherichia coli strain (OD259). The Hsp40 chimeras containing J-domains originating from soluble (cytosolic or endoplasmic reticulum (ER)-lumenal) Hsp40s were able to reverse the thermosensitivity of E. coli OD259. In all cases, modified derivatives of these chimeric proteins containing an His to Gln substitution in the HPD motif of the J-domain were unable to reverse the thermosensitivity of E. coli OD259. This suggested that these J-domains exerted their in vivo functionality through a specific interaction with E. coli Hsp70, DnaK. Interestingly, a Hsp40 chimera containing the J-domain of ERj1, an integral membrane-bound ER Hsp40, was unable to reverse the thermosensitivity of E. coli OD259, suggesting that this J-domain was unable to functionally interact with DnaK. Substitutions of conserved amino acid residues and motifs were made in all four helices (I-IV) and the loop regions of the J-domains, and the modified chimeric Hsp40s were tested for functionality using the in vivo assay. Substitution of a highly conserved basic residue in helix II of the J-domain was found to disrupt in vivo functionality for all the J-domains tested. We propose that helix II and the HPD motif of the J-domain represent the fundamental elements of a binding surface required for the interaction of Hsp40s with Hsp70s, and that this surface has been conserved in mammalian, parasitic and bacterial systems. 相似文献