全文获取类型
收费全文 | 337篇 |
免费 | 37篇 |
专业分类
374篇 |
出版年
2022年 | 2篇 |
2021年 | 2篇 |
2020年 | 2篇 |
2018年 | 6篇 |
2017年 | 4篇 |
2016年 | 13篇 |
2015年 | 16篇 |
2014年 | 10篇 |
2013年 | 11篇 |
2012年 | 24篇 |
2011年 | 26篇 |
2010年 | 15篇 |
2009年 | 10篇 |
2008年 | 24篇 |
2007年 | 21篇 |
2006年 | 22篇 |
2005年 | 21篇 |
2004年 | 21篇 |
2003年 | 20篇 |
2002年 | 18篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1992年 | 3篇 |
1991年 | 4篇 |
1990年 | 4篇 |
1988年 | 2篇 |
1987年 | 6篇 |
1986年 | 5篇 |
1985年 | 3篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1979年 | 2篇 |
1975年 | 3篇 |
1972年 | 4篇 |
1970年 | 3篇 |
1967年 | 5篇 |
1964年 | 3篇 |
1962年 | 1篇 |
1953年 | 1篇 |
1952年 | 1篇 |
1950年 | 1篇 |
1941年 | 1篇 |
1939年 | 1篇 |
1938年 | 1篇 |
1936年 | 2篇 |
1935年 | 1篇 |
排序方式: 共有374条查询结果,搜索用时 9 毫秒
1.
2.
Proteolytic cleavage of IgG and other protein substrates by Dirofilaria immitis microfilarial enzymes 总被引:1,自引:0,他引:1
Proteases were detected in aqueous extracts of Dirofilaria immitis microfilariae. Enzymes within the extract were capable of hydrolyzing Azocoll, a general protease substrate, at pH's 7, 8, and 9. Sensitivities to a variety of protease inhibitors indicated that multiple azocollytic enzymes were present in the extract, most prominent of which appear to belong to the serine class of proteases. By incorporating various substrates into the matrices of polyacrylamide gels, 2 SDS-resistant, mercaptoethanol-sensitive proteases in the MF extract were identified at 22 and 76 kDa. These proteases showed differential abilities to digest casein, fibrinogen, hemoglobin, and IgG. The MF extract hydrolyzed radiolabeled IgG into 8-10-kDa fragments following a 20-hr incubation. A similar degree of digestion was observed in 2 hr when viable microfilariae were used. The potential significance of these proteases in the evasion of host effector mechanisms is discussed. 相似文献
3.
Cellular transformation, tyrosine kinase oncogenes, and the cellular adhesion plaque 总被引:7,自引:0,他引:7
S Kellie 《BioEssays : news and reviews in molecular, cellular and developmental biology》1988,8(1):25-30
The study of adhesion plaques in normal and transformed cells provides a series of phenotypic markers by which the process of transformation can be followed. Several proteins which are concentrated in adhesion plaques have now been identified; a few of these can act as targets for tyrosine kinase. In an attempt to characterize the relationship between tyrosine phosphorylation and cell transformation, the reactions of three such proteins – vinculin, talin and integrin – with a range of tyrosine kinase oncogene products have been studied in detail. 相似文献
4.
Pretreatment of human neutrophils with recombinant tumour necrosis factor-alpha (rTNF-alpha) and/or interleukin-8 (rIL-8), but not with either transforming growth factor-beta, interleukin-6 or interferon-gamma, rendered these cells less responsive to FMLP, in microchemotaxis assays. This inhibitory effect was dose dependent and more powerful when neutrophils were pretreated with a mixture of both cytokines. Intravenous injection of human rIL-8 (hrIL-8) and/or murine rTNF-alpha (mrTNF-alpha) also significantly reduced in vivo neutrophil migration into peritoneal cavities of rats stimulated with carrageenan. These data suggest that the defect in neutrophil migration during septicaemia or endotoxaemia may be the result of the continuous release of IL-8 and TNF-alpha into the circulation. Thus, either the selective control or blockade of releasing of these cytokines as well as of its effects on neutrophils may be clinically useful in reestablishing the cell defence mechanisms. 相似文献
5.
Terminal structure and heterogeneity in human cytomegalovirus strain AD169. 总被引:15,自引:12,他引:3
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
We have characterized the heterogeneity occurring at the junction of the long (L) and short (S) segments and at the termini of the strain AD169 human cytomegalovirus (HCMV) genome by restriction endonuclease mapping and nucleotide sequence analyses. The HCMV a sequence was identified by its position at both termini and inverted orientation at the L-S junction. Heterogeneity at both termini and the L-S junction was generated by the presence of fused and tandem a sequences. Some S termini lacked an a sequence. In addition, near the L terminus and at the L-S junction there were a variable number of 217-base-pair (bp) XhoI fragments arranged in tandem. The 217-bp fragments consisted of a portion of the a and adjacent b sequences (in the L-segment repeat) bounded by the same direct repeats (DR1) found at the boundaries of the a sequence. A model for the generation of these heterogeneous fragments is presented. We also determined the sequence of seven cloned terminal fragments, five from the L terminus and two from the S terminus. All L termini contained identical terminal sequences ending with base 32 of a 33-bp DR1. The S termini differed from each other and from the L-segment termini. One S terminus lacked an a sequence and terminated within S-segment repeat (c) sequences. The second S terminus contained an a sequence and terminated with bases 20 to 33 of a 33-bp DR1. A comparison of the cloned L and S terminal sequences with cloned L-S junction sequences suggested that the termini contained 3' single base extensions which were removed during the cloning. We also show that the herpesvirus conserved sequence is in a similar position relative to the termini of HCMV and several other herpesviruses, thus adding further support for the role of the sequence in the maturation of viral DNA. 相似文献
6.
Interaction of tumour promoters with epithelial cells in culture : An immunofluorescence study 总被引:8,自引:0,他引:8
12-O-tetradecanoyl phorbol-13-acetate (TPA) has a profound and rapid influence on the cytoskeleton of Madin-Darby Canine Kidney (MDCK) cells. Within 10 min, TPA induces a rapid change in morphology, from a flat, cuboidal state to a rounded or elongated morphology in which the cell membranes become convoluted. Concomitant with this morphological change is a rapid dissolution of stress fibres and a redistribution of F-actin from microfilament bundles to a membrane or sub-membranous location. The rearrangement of actin is paralleled by a rearrangement of alpha-actinin and a reduction in the number of vinculin-containing adhesion plaques. Unusual F-actin configurations are often found emanating from a perinuclear location, usually containing alpha-actinin and terminating in a vinculin-containing adhesion plaque. The cytoskeletal rearrangements occur in the presence of inhibitors of protein synthesis or oxidative phosphorylation, but do not occur if glycolysis is also inhibited. The rearrangements are partly abrogated by the presence of cytochalasin B (CB). Despite these dramatic changes in microfilaments the polymerization state of actin remained unaltered after TPA treatment. Furthermore, although changes in the movement of membrane lipids have been reported, no obvious differences in the ability of glycoproteins to redistribute in the plane of the membrane were found as judged by FITC-concanavalin A (conA) induced patching. The rapidity of the morphological response of MDCK cells to TPA indicates that the cytoskeleton is one of the primary targets of TPA, but that tumour promoters differ from RNA tumour viruses in their effect on the state of actin polymerization. 相似文献
7.
The gas–liquid chromatography of carboxylic acid esters of the urinary 11-deoxy-17-oxo steroids: Determination as n-butyrates
下载免费PDF全文
![点击此处可从《The Biochemical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
1. The gas-liquid-chromatographic separations of the acetate, propionate, n-butyrate, isobutyrate and n-valerate esters of androsterone, aetiocholanolone and dehydroepiandrosterone were studied on a 1% neopentyl glycol sebacate column. The n-butyrate, isobutyrate and n-valerate esters were well resolved. 2. The three steroids derived from hydrolysed urinary 17-oxo steroid conjugate extracts were analysed by gas-liquid chromatography after conversion into their n-butyrate esters. The results were compared with independent determinations involving chromatography on alumina. 相似文献
8.
Cecilio CA Costa EH Ucelli P Chaves CA Toffoli MC Flores CA Cunha FQ Ferreira SH Tamashiro WM 《Mediators of inflammation》1997,6(1):46-52
Macrophages harvested from the peritoneal cavities of rats release a neutrophil chemotactic factor (MNCF) in response to stimulation with Gram-negative bacterial lipopolysaccharide (LPS). MNCF has been shown to be active in rats treated with dexamethasone, a glucocorticoid that usually inhibits the neutrophil migration induced in this species by interleukin (IL)-1, tumour necrosis factor alpha (TNFalpha), IL-8, C5a and leukotriene B(4) (LTB(4)). Here we report that macrophages harvested from peritoneal cavities of mice, and stimulated in vitro with LPS, also release a factor that induces neutrophil migration in dexamethasone-treated animals. This chemotactic activity was neutralized by the incubation of the LPS-stimulated macrophage supernatants with a purified polyclonal IgG anti-mouse TNFalpha. In addition, significant amounts of TNF were detected in the supernatants. The neutrophil migration induced by intraperitoneal administration of recombinant murine TNFalpha was also unaffected by pretreatment of the mice with dexamethasone. Moreover, neutrophil migration induced by intraperitoneal injection of LPS was completely blocked by pretreatment of the mice with a monoclonal antibody against murine TNFalpha. In conclusion, our results support the hypothesis that, in contrast to the role of TNF in rats (where it indirectly induces neutrophil migration), in mice, it may be an important mediator in the recruitment of neutrophils to inflammatory sites. 相似文献
9.
André-Denis G. Wright Andrew J. Williams Barbara Winder Claus T. Christophersen Sharon L. Rodgers Kellie D. Smith 《Applied microbiology》2004,70(3):1263-1270
The molecular diversity of rumen methanogens in sheep in Australia was investigated by using individual 16S rRNA gene libraries prepared from the rumen contents obtained from six merino sheep grazing pasture (326 clones), six sheep fed an oaten hay-based diet (275 clones), and five sheep fed a lucerne hay-based diet (132 clones). A total of 733 clones were examined, and the analysis revealed 65 phylotypes whose sequences (1,260 bp) were similar to those of cultivated methanogens belonging to the order Methanobacteriales. Pasture-grazed sheep had more methanogen diversity than sheep fed either the oaten hay or lucerne hay diet. Methanobrevibacter strains SM9, M6, and NT7 accounted for over 90% of the total number of clones identified. M6 was more prevalent in grazing sheep, and SM9, despite being found in 16 of the 17 sheep, was more prevalent in sheep fed the lucerne-based diet. Five new species were identified. Two of these species exhibited very little sequence similarity to any cultivated methanogens and were found eight times in two of the six sheep that were grazing pasture. These unique sequences appear to represent a novel group of rumen archaea that are atypical for the rumen environment. 相似文献
10.
Sandra D. Taylor Kristine K. Barlow‐Stewart Susan A. Treloar Mark Stranger Kellie Chenoweth 《New genetics and society》2013,32(2):225-239
Genetic discrimination, defined as the differential treatment of individuals or their relatives on the basis of actual or presumed genetic differences, is an emerging issue of interest in academic, clinical, social and legal contexts. While its potential significance has been discussed widely, verified empirical data are scarce. Genetic discrimination is a complex phenomenon to describe and investigate, as evidenced by the recent Australian Law Reform Commission inquiry in Australia. The authors research project, which commenced in 2002, aims to document the multiple perspectives and experiences regarding genetic discrimination in Australia and inform future policy development and law reform. Data are being collected from consumers, employers, insurers and the legal system. Attempted verification of alleged accounts of genetic discrimination will be a novel feature of the research. This paper overviews the early stages of the research, including conceptual challenges and their methodological implications. 相似文献