全文获取类型
收费全文 | 130篇 |
免费 | 0篇 |
专业分类
系统科学 | 8篇 |
理论与方法论 | 1篇 |
现状及发展 | 35篇 |
研究方法 | 12篇 |
综合类 | 74篇 |
出版年
2019年 | 1篇 |
2014年 | 1篇 |
2012年 | 6篇 |
2011年 | 6篇 |
2010年 | 2篇 |
2009年 | 3篇 |
2008年 | 8篇 |
2007年 | 3篇 |
2006年 | 3篇 |
2005年 | 4篇 |
2004年 | 3篇 |
2003年 | 3篇 |
2002年 | 3篇 |
2001年 | 3篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 1篇 |
1996年 | 1篇 |
1994年 | 1篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 8篇 |
1976年 | 4篇 |
1975年 | 9篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1971年 | 1篇 |
1970年 | 6篇 |
1969年 | 5篇 |
1968年 | 6篇 |
1967年 | 1篇 |
1965年 | 1篇 |
1964年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有130条查询结果,搜索用时 953 毫秒
1.
P. Levy G. Cherqui A. Robert D. Wicek J. Picard 《Cellular and molecular life sciences : CMLS》1989,45(6):588-591
Summary During the spontaneous differentiation (day 5 to day 15 of the culture) of Caco-2 cells, the sulfation of cell layer glycosaminoglycans increased, whereas protein kinase C activity was concomitantly redistributed from the membrane to the cytosol. The protein kinase C activators, 4-phorbol 12-myristate, 13-acetate and 1,2-dioctanoyl-glycerol inhibited glycosaminoglycan sulfation. By contrast, 4-phorbol 12, 13 didecanoate was ineffective.These results suggest that membrane-bound PKC may exert a modulatory effect on glycosaminoglycan sulfation, and this effect is gradually attenuated as Caco-2 cell differentiation progresses. 相似文献
2.
Summary The ability of liposomes composed of different kinds of phospholipid materials to adhere to the surface of the cornea was studied in the rabbit. The liposomes were labelled with tracer amounts of an I125-labelled phosphatidylethanolamine derivative and were instilled in 10 l drops onto the cornea. The retention of radioactivity was monitored. The results show that liposomes containing positively charged phospholipids are better retained than an albumin control. Thus, it may be possible to develop a drug delivery, liposome system which would permit long-term sustained release of ophthalmic drugs onto the cornea. 相似文献
3.
Inga Sandler Nitzan Zigdon Efrat Levy Amir Aharoni 《Cellular and molecular life sciences : CMLS》2014,71(4):673-682
Computational approaches for detecting co-evolution in proteins allow for the identification of protein–protein interaction networks in different organisms and the assignment of function to under-explored proteins. The detection of co-variation of amino acids within or between proteins, moreover, allows for the discovery of residue–residue contacts and highlights functional residues that can affect the binding affinity, catalytic activity, or substrate specificity of a protein. To explore the functional impact of co-evolutionary changes in proteins, a combined experimental and computational approach must be recruited. Here, we review recent studies that apply computational and experimental tools to obtain novel insight into the structure, function, and evolution of proteins. Specifically, we describe the application of co-evolutionary analysis for predicting high-resolution three-dimensional structures of proteins. In addition, we describe computational approaches followed by experimental analysis for identifying specificity-determining residues in proteins. Finally, we discuss studies addressing the importance of such residues in terms of the functional divergence of proteins, allowing proteins to evolve new functions while avoiding crosstalk with existing cellular pathways or forming reproductive barriers and hence promoting speciation. 相似文献
4.
Tumour evolution inferred by single-cell sequencing 总被引:1,自引:0,他引:1
Navin N Kendall J Troge J Andrews P Rodgers L McIndoo J Cook K Stepansky A Levy D Esposito D Muthuswamy L Krasnitz A McCombie WR Hicks J Wigler M 《Nature》2011,472(7341):90-94
Genomic analysis provides insights into the role of copy number variation in disease, but most methods are not designed to resolve mixed populations of cells. In tumours, where genetic heterogeneity is common, very important information may be lost that would be useful for reconstructing evolutionary history. Here we show that with flow-sorted nuclei, whole genome amplification and next generation sequencing we can accurately quantify genomic copy number within an individual nucleus. We apply single-nucleus sequencing to investigate tumour population structure and evolution in two human breast cancer cases. Analysis of 100 single cells from a polygenomic tumour revealed three distinct clonal subpopulations that probably represent sequential clonal expansions. Additional analysis of 100 single cells from a monogenomic primary tumour and its liver metastasis indicated that a single clonal expansion formed the primary tumour and seeded the metastasis. In both primary tumours, we also identified an unexpectedly abundant subpopulation of genetically diverse 'pseudodiploid' cells that do not travel to the metastatic site. In contrast to gradual models of tumour progression, our data indicate that tumours grow by punctuated clonal expansions with few persistent intermediates. 相似文献
5.
Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm 总被引:2,自引:0,他引:2
ME Lindsay D Schepers NA Bolar JJ Doyle E Gallo J Fert-Bober MJ Kempers EK Fishman Y Chen L Myers D Bjeda G Oswald AF Elias HP Levy BM Anderlid MH Yang EM Bongers J Timmermans AC Braverman N Canham GR Mortier HG Brunner PH Byers J Van Eyk L Van Laer HC Dietz BL Loeys 《Nature genetics》2012,44(8):922-927
Loeys-Dietz syndrome (LDS) associates with a tissue signature for high transforming growth factor (TGF)-β signaling but is often caused by heterozygous mutations in genes encoding positive effectors of TGF-β signaling, including either subunit of the TGF-β receptor or SMAD3, thereby engendering controversy regarding the mechanism of disease. Here, we report heterozygous mutations or deletions in the gene encoding the TGF-β2 ligand for a phenotype within the LDS spectrum and show upregulation of TGF-β signaling in aortic tissue from affected individuals. Furthermore, haploinsufficient Tgfb2(+/-) mice have aortic root aneurysm and biochemical evidence of increased canonical and noncanonical TGF-β signaling. Mice that harbor both a mutant Marfan syndrome (MFS) allele (Fbn1(C1039G/+)) and Tgfb2 haploinsufficiency show increased TGF-β signaling and phenotypic worsening in association with normalization of TGF-β2 expression and high expression of TGF-β1. Taken together, these data support the hypothesis that compensatory autocrine and/or paracrine events contribute to the pathogenesis of TGF-β-mediated vasculopathies. 相似文献
6.
An AIDS-related cytotoxic autoantibody reacts with a specific antigen on stimulated CD4+ T cells 总被引:2,自引:0,他引:2
R B Stricker T M McHugh D J Moody W J Morrow D P Stites M A Shuman J A Levy 《Nature》1987,327(6124):710-713
Patients with the acquired immune deficiency syndrome (AIDS) and AIDS-related conditions are known to have abnormalities of T cell subpopulations, including a decreased helper/inducer (bearing the CD4 antigen) to suppressor/cytotoxic (bearing the CD8 antigen) T cell ratio and decreased absolute numbers of T cells with the CD4+ phenotype. Infection of T cells with a retrovirus, termed human immunodeficiency virus (HIV), is thought to be important in these abnormalities. HIV infection alone does not adequately explain the CD4+ T-cell abnormalities seen in AIDS, however, and the nature of T-cell destruction in this disease remains poorly characterized. Here we describe an AIDS-related serum autoantibody that reacts with an antigen of relative molecular mass 18,000 (Mr 18K) restricted to lectin-stimulated or HIV-infected CD4+ T cells. The antibody also suppresses proliferation of CD4+ T cells in vitro and induces cytotoxicity of these cells in the presence of complement. Its role in the development of AIDS merits attention. 相似文献
7.
Molecular basis of triclosan activity 总被引:19,自引:0,他引:19
Levy CW Roujeinikova A Sedelnikova S Baker PJ Stuitje AR Slabas AR Rice DW Rafferty JB 《Nature》1999,398(6726):383-384
8.
Polyisoprenyl phosphates: natural antiinflammatory lipid signals 总被引:1,自引:0,他引:1
Lipoxins (LX) and aspirin-triggered 15-epimer LX are leukocyte-derived eicosanoids generated during host defense that serve
as down-regulatory signals. The specific intracellular events that govern cellular responses to inhibitory extracellular signals
are of wide interest in order to understand pivotal intracellular events in diseases characterized by enhanced inflammatory
responses, such as asthma, rheumatoid arthritis and atherosclerosis. We recently uncovered a novel role for polyisoprenyl
phosphates, in particular presqualene diphosphate (PSDP), as natural down-regulatory signals in human neutrophils that directly
inhibit phospholipase D and superoxide anion generation. Activation of LXA4 receptors (ALXR) reverses proinflammatory receptor-initiated decrements in PSDP and inhibits cellular responses. These findings
represent evidence for a novel paradigm for lipid-protein interactions in the control of cellular responses, namely receptor-initiated
degradation of repressor lipids that is subject to regulation by aspirin treatment via the actions of aspirin-triggered 15-epimer
LX at the ALXR, and identify new templates for antiinflammatory drugs by design. 相似文献
9.
Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium 总被引:12,自引:0,他引:12
Smahi A Courtois G Vabres P Yamaoka S Heuertz S Munnich A Israël A Heiss NS Klauck SM Kioschis P Wiemann S Poustka A Esposito T Bardaro T Gianfrancesco F Ciccodicola A D'Urso M Woffendin H Jakins T Donnai D Stewart H Kenwrick SJ Aradhya S Yamagata T Levy M Lewis RA Nelson DL 《Nature》2000,405(6785):466-472
10.
The ability of liposomes composed of different kinds of phospholipid materials to adhere to the surface of the cornea was studied in the rabbit. The liposomes were labelled with tracer amounts of an I125-labelled phosphatidylethanolamine derivative and were instilled in 10 microliters drops onto the cornea. The retention of radioactivity was monitored. The results show that liposomes containing positively charged phospholipids are better retained than an albumin control. Thus, it may be possible to develop a drug delivery liposome system which would permit long-term sustained release of ophthalmic drugs onto the cornea. 相似文献