全文获取类型
收费全文 | 173篇 |
免费 | 12篇 |
专业分类
185篇 |
出版年
2018年 | 2篇 |
2016年 | 1篇 |
2015年 | 4篇 |
2014年 | 4篇 |
2013年 | 8篇 |
2012年 | 10篇 |
2011年 | 5篇 |
2010年 | 7篇 |
2009年 | 4篇 |
2008年 | 17篇 |
2007年 | 9篇 |
2006年 | 7篇 |
2005年 | 6篇 |
2004年 | 4篇 |
2003年 | 4篇 |
2002年 | 9篇 |
2001年 | 8篇 |
2000年 | 4篇 |
1999年 | 4篇 |
1998年 | 5篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1992年 | 6篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1987年 | 6篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1982年 | 3篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 5篇 |
1973年 | 3篇 |
1936年 | 1篇 |
1928年 | 1篇 |
1927年 | 1篇 |
1922年 | 2篇 |
1918年 | 2篇 |
1916年 | 1篇 |
1915年 | 1篇 |
排序方式: 共有185条查询结果,搜索用时 0 毫秒
1.
2.
J Collinge M S Palmer T Campbell K C Sidle D Carroll A Harding 《BMJ (Clinical research ed.)》1993,306(6873):301-302
OBJECTIVE--To identify cases of inherited prion diseases in Britain and to assess their phenotypic features. DESIGN--Screening study of patients suspected clinically to have Creutzfeldt-Jakob disease and other neurodegenerative diseases by prion protein gene analysis. SETTING--Biochemical research department. SUBJECTS--Patients suspected to have Creutzfeldt-Jakob disease and other neurodegenerative diseases. RESULTS--Two patients with symptoms characteristic of sporadic Creutzfeldt-Jakob disease were found to have inherited prion protein disease (PrP lysine 200), with a mutation at codon 200 of the prion protein gene. Both were homozygous at codon 129 of the gene. One patient was a man aged 58 of British descent while the other was of Libyan Jewish origin. CONCLUSION--Two foci of inherited prion disease are known, among Libyan Jews and in Slovakia. A separate British focus of the disease may also exist. Heterozygosity at codon 129 may lead to reduced penetrance of the mutation. 相似文献
3.
Colonies of Sordaria brevicollis cut with a razor blade were examined and compared to undamaged control colonies using light and transmission electron microscopy. Cut hyphae lost cytoplasm from severed compartments but retained cytoplasm in adjacent compartments due to the plugging of septal pores by nuclei. Hexagonal crystals were observed in hyphae but were neither positioned near to septal pores nor observed plugging them. Approximately 36% of setpal pores in undamaged hyphae were found to contain a nucleus, presumably migrating through them. It is suggested that nuclei plug septal pores in severed hyphae of S. brevicollis because they are more conveniently positioned to do so than the distant hexagonal crystals. 相似文献
4.
Colonies of Penicillium chrysogenum (Thom) Wisconsin strain Q176 were fixed at varying time intervals after having been severed with a razor blade and were examined by transmission electron microscopy. Within such colonies Woronin bodies were found to have plugged septal pores on either side of the cut, both towards and away from the hyphal apices. A very close association of Woronin bodies with septa was retained in damaged compartments emptied of virtually all other contents. In colonies fixed 3 h after cutting, deposition of material over the plugged pores occurred on the side of the septum away from the cut. The newly deposited material was similar in appearance to hyphal wall and septal plate constituents. This consolidation of the seal was apparently completed within 3 h because no further change was observed in colonies fixed 17 h after cutting. 相似文献
5.
Summary We investigated the effects of genotype, habitat, and seasonal variation on production of the iridoid glycosides, aucubin and catalpol, in leaves of the common weed Plantago lanceolata. Two genotypes, one each from a lawn and an adjacent abandoned hayfield population, were clonally replicated in the greenhouse, and then planted back into the two habitats. One quarter of the plants from each treatment were harvested on each of four dates, at approximately two-week intervals. Over the course of the growing season, and in both habitats, we found a significant increase in the concentration of both aucubin and catalpol in P. lanceolata leaves. The genotypes differed in their response to environmental variation, both in time and between sites, as indicated by significant genotype x date and genotype x site interactions. Early in the season, habitat (lawn or field) had a greater effect on iridoid glycoside concentration than did plant genotype, but later in the season, plant genotype was more influential in determining the iridoid glycoside concentration. Thus, the relative palatability of Plantago genotypes to specialist and generalist herbivores may vary in time and space. 相似文献
6.
7.
Src kinase mediates phosphatidylinositol 3-kinase/Akt-dependent rapid endothelial nitric-oxide synthase activation by estrogen 总被引:13,自引:0,他引:13
Haynes MP Li L Sinha D Russell KS Hisamoto K Baron R Collinge M Sessa WC Bender JR 《The Journal of biological chemistry》2003,278(4):2118-2123
17beta-Estradiol activates endothelial nitric oxide synthase (eNOS), enhancing nitric oxide (NO) release from endothelial cells via the phosphatidylinositol 3-kinase (PI3-kinase)/Akt pathway. The upstream regulators of this pathway are unknown. We now demonstrate that 17beta-estradiol rapidly activates eNOS through Src kinase in human endothelial cells. The Src family kinase specific-inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) abrogates 17beta-estradiol- but not ionomycin-stimulated NO release. Consistent with these results, PP2 blocked 17beta-estradiol-induced Akt phosphorylation but did not inhibit NO release from cells transduced with a constitutively active Akt. PP2 abrogated 17beta-estradiol-induced activation of PI3-kinase, indicating that the PP2-inhibitable kinase is upstream of PI3-kinase and Akt. A 17beta-estradiol-induced estrogen receptor/c-Src association correlated with rapid c-Src phosphorylation. Moreover, transfection of kinase-dead c-Src inhibited 17beta-estradiol-induced Akt phosphorylation, whereas constitutively active c-Src increased basal Akt phosphorylation. Estrogen stimulation of murine embryonic fibroblasts with homozygous deletions of the c-src, fyn, and yes genes failed to induce Akt phosphorylation, whereas cells maintaining c-Src expression demonstrated estrogen-induced Akt activation. Estrogen rapidly activated c-Src inducing an estrogen receptor, c-Src, and P85 (regulatory subunit of PI3-kinase) complex formation. This complex formation results in the successive activation of PI3-kinase, Akt, and eNOS with consequent enhanced NO release, implicating c-Src as a critical upstream regulator of the estrogen-stimulated PI3-kinase/Akt/eNOS pathway. 相似文献
8.
Clarke AR Jackson GS Collinge J 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2001,356(1406):185-195
Prion diseases such as Creutzfeldt-Jakob disease (CJD) in humans and scrapie and bovine spongiform encephalopathy (BSE) in animals are associated with the accumulation in affected brains of a conformational isomer (PrP(Sc)) of host-derived prion protein (PrP(C)). According to the protein-only hypothesis, PrP(Sc) is the principal or sole component of transmissible prions. The conformational change known to be central to prion propagation, from a predominantly alpha-helical fold to one predominantly comprising beta structure, can now be reproduced in vitro, and the ability of beta-PrP to form fibrillar aggregates provides a plausible molecular mechanism for prion propagation. The existence of multiple prion strains has been difficult to explain in terms of a protein-only infectious agent but recent studies of human prion diseases suggest that strain-specific phenotypes can be encoded by different PrP conformations and glycosylation patterns. The experimental confirmation that a novel form of human prion disease, variant CJD, is caused by the same prion strain as cattle BSE, has highlighted the pressing need to understand the molecular basis of prion propagation and the transmission barriers that limit their passage between mammalian species. These and other advances in the fundamental biology of prion propagation are leading to strategies for the development of rational therapeutics. 相似文献
9.
Post-natal knockout of prion protein alters hippocampal CA1 properties, but does not result in neurodegeneration 总被引:14,自引:0,他引:14
Mallucci GR Ratté S Asante EA Linehan J Gowland I Jefferys JG Collinge J 《The EMBO journal》2002,21(3):202-210
Prion protein (PrP) plays a crucial role in prion disease, but its physiological function remains unclear. Mice with gene deletions restricted to the coding region of PrP have only minor phenotypic deficits, but are resistant to prion disease. We generated double transgenic mice using the Cre-loxP system to examine the effects of PrP depletion on neuronal survival and function in adult brain. Cre-mediated ablation of PrP in neurons occurred after 9 weeks. We found that the mice remained healthy without evidence of neurodegeneration or other histopathological changes for up to 15 months post-knockout. However, on neurophysiological evaluation, they showed significant reduction of afterhyperpolarization potentials (AHPs) in hippocampal CA1 cells, suggesting a direct role for PrP in the modulation of neuronal excitability. These data provide new insights into PrP function. Furthermore, they show that acute depletion of PrP does not affect neuronal survival in this model, ruling out loss of PrP function as a pathogenic mechanism in prion disease and validating therapeutic approaches targeting PrP. 相似文献
10.