全文获取类型
收费全文 | 163篇 |
免费 | 42篇 |
出版年
2023年 | 1篇 |
2021年 | 1篇 |
2018年 | 2篇 |
2017年 | 5篇 |
2016年 | 2篇 |
2015年 | 6篇 |
2014年 | 8篇 |
2013年 | 8篇 |
2012年 | 9篇 |
2011年 | 12篇 |
2010年 | 6篇 |
2009年 | 4篇 |
2008年 | 9篇 |
2007年 | 12篇 |
2006年 | 8篇 |
2005年 | 7篇 |
2004年 | 11篇 |
2003年 | 7篇 |
2002年 | 8篇 |
2001年 | 8篇 |
2000年 | 10篇 |
1999年 | 7篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1968年 | 1篇 |
1964年 | 2篇 |
1962年 | 1篇 |
排序方式: 共有205条查询结果,搜索用时 15 毫秒
61.
Reasons for the different levels of 5-methyl cytosine encountered in the DNA of two baby hamsters kidney fibroblast lines, BHK-21/C13 and BHK-21/PyY have been investigated. From enzymic studies it does not seem that there are large numbers of potentially methylatable cytosine residues in the C13 line DNA which contains a lower level of 5-methyl cytosine. Rather it is possible that the difference may be due to the reiteration in the PyY strain of certain sequences containing 5-methyl cytosine which simply occur less frequently in the other line. 相似文献
62.
L Ortiz P Aza-Blanc M Zannini A C Cato P Santisteban 《The Journal of biological chemistry》1999,274(21):15213-15221
63.
64.
A unique cell, the tip mother cell, arises in the primordium of each Drosophila Malpighian tubule by lateral inhibition within a cluster of achaete-expressing cells. This cell maintains achaete expression and divides to produce daughters of equivalent potential, of which only one, the tip cell, adopts the primary fate and continues to express achaete, while in the other, the sibling cell, achaete expression is lost (M. Hoch et al., 1994, Development 120, 3439-3450). In this paper we chart the mechanisms by which achaete expression is differentially maintained in the tip cell lineage to stabilise cell fate. First, wingless is required to maintain the expression of achaete in the tubule primordium so that wingless mutants lack tip cells. Conversely, increasing wingless expression results in the persistence of achaete expression in the cell cluster. Second, Notch signalling is restricted by the asymmetric segregation of Numb, as the tip mother cell divides, so that achaete expression is maintained only in the tip cell. In embryos mutant for Notch tip cells segregate at the expense of sibling cells, whereas in numb neither daughter cell adopts the tip cell fate resulting in tubules with two sibling cells. Conversely, when numb is overexpressed two tip cells segregate and tubules have no sibling cells. Analysis of cell proliferation in the developing tubules of embryos lacking Wingless after the critical period for tip cell allocation reveals an additional requirement for wingless for the promotion of cell division. In contrast, alteration in the expression of numb has no effect on the final tubule cell number. 相似文献
65.
Taurine is an important osmolyte involved in cell volume regulation. During regulatory volume decrease it is released via a volume-sensitive organic osmolyte/anion channel. Several molecules have been suggested as candidates for osmolyte release. In this study, we chose three of these, namely ClC-2, ClC-3 and ICln, because of their expression in rat astrocytes, a cell type which is known to release taurine under hypotonic stress, and their activation by hypotonic shock. As all three candidates were also suggested to be chloride channels, we investigated their permeability for both chloride and taurine under isotonic and hypotonic conditions using the Xenopus laevis oocyte expression system. We found a volume-sensitive increase of chloride permeability in ClC-2-expressing oocytes only. Yet, the taurine permeability was significantly increased under hypotonic conditions in oocytes expressing any of the tested candidates. Further experiments confirmed that the detected taurine efflux does not represent unspecific leakage. These results suggest that ClC-2, ClC-3 and ICln either participate in taurine transport themselves or upregulate an endogenous oocyte osmolyte channel. In either case, the taurine efflux of oocytes not being accompanied by an increased chloride flux suggests that taurine and chloride can be released via two separate pathways. 相似文献
66.
Schneikert J Hübner S Langer G Petri T Jäättelä M Reed J Cato AC 《The EMBO journal》2000,19(23):6508-6516
Receptor-associating protein 46 (RAP46) is a cochaperone that regulates the transactivation function of several steroid receptors. It is transported into the nucleus by a liganded glucocorticoid receptor where it downregulates DNA binding and transactivation by this receptor. The N- and C-termini of RAP46 are both implicated in its negative regulatory function. In metabolic labelling experiments, we have shown that the N-terminus of RAP46 is modified by phosphorylation, but this does not contribute to the downregulation of glucocorticoid receptor activity. However, deletion of a sequence that binds 70 kDa heat shock protein (Hsp70) and the constitutive isoform of Hsp70 (Hsc70) at the C-terminus of RAP46 abrogated its negative regulatory action. Surface plasmon resonance studies showed that RAP46 binds the glucocorticoid receptor only when it has interacted with Hsp70/Hsc70, and confocal immunofluorescence analyses revealed a nuclear transport of Hsp70/Hsc70 by the liganded receptor. Together these findings demonstrate an important contribution of Hsp70/Hsc70 in the binding of RAP46 to the glucocorticoid receptor and suggest a role for this molecular chaperone in the RAP46-mediated downregulation of glucocorticoid receptor activity. 相似文献
67.
Brede DA Faye T Stierli MP Dasen G Theiler A Nes IF Meile L Holo H 《Applied and environmental microbiology》2005,71(12):8077-8084
Heterologous bacteriocin production in Propionibacterium freudenreichii is described. We developed an efficient system for DNA shuttling between Escherichia coli and P. freudenreichii using vector pAMT1. It is based on the P. freudenreichii rolling-circle replicating plasmid pLME108 and carries the cml(A)/cmx(A) chloramphenicol resistance marker. Introduction of the propionicin T1 structural gene (pctA) into pAMT1 under the control of the constitutive promoter (P4) yielded bacteriocin in amounts equal to those of the wild-type producer Propionibacterium thoenii 419. The P. freudenreichii clone showed propionicin T1 activity in coculture, killing 90% of sensitive bacteria within 48 h. The pamA gene from P. thoenii 419 encoding the protease-activated antimicrobial peptide (PAMP) was cloned and expressed in P. freudenreichii, resulting in secretion of the pro-PAMP protein. Like in the wild type, PAMP activation was dependent on externally added protease. Secretion of the antimicrobial peptide was obtained from a clone in which the pamA signal peptide and PAMP were fused in frame. The promoter region of pamA was identified by fusion of putative promoter fragments to the coding sequence of the pctA gene. The P4 and Ppamp promoters directed constitutive gene expression, and activity of both promoters was enhanced by elements upstream of the promoter core region. 相似文献
68.
Ferreri C Kratzsch S Brede O Marciniak B Chatgilialoglu C 《Free radical biology & medicine》2005,38(9):1180-1187
Trans lipids in humans originate exogenously from the ingestion of isomerized fats. An endogenous path comprising a thiyl radical-catalyzed cis-trans isomerization of cis-unsaturated phospholipids was proposed. However, whether an isomerization process might be feasible in eukaryotic cells remained to be established. Here we report the presence of trans lipids in human monocytic leukemia cell membranes (THP-1) before and after treatment with a 10 mM series of thiols. Oleic, linoleic, and arachidonic acid residues of membrane phospholipids were analyzed and, unexpectedly, an initial trans lipid content was found in control cells. Then, incubation for 24 h with thiols under physiological conditions slightly increased trans lipid content. Formation of trans isomers was also evaluated in the presence of thiol and under free radical stress induced by gamma-irradiation or by thermal decomposition of azo-compounds. The similarity of isomer trends formed under incubation and stress conditions, together with the reactivity order of fatty acid residues (arachidonic > linoleic approximately oleic), indicated a common radical path and some mechanistic considerations are advanced. These results offer the first evidence that trans lipids are formed in eukaryotic cells and confirm that thiyl radicals are harmful to the integrity of cis lipid geometry. This work motivates further studies into the relationship between lipid isomerization outcome and thiyl radicals in cellular systems, as well as the formation of trans lipids and the metabolic response to such a perturbation introduced into biological membranes. 相似文献
69.
Transgenic mouse models of angiotensin receptor subtype function in the cardiovascular system 总被引:2,自引:0,他引:2
Angiotensin II mediates is biological actions via different subtypes of G protein-coupled receptors, termed AT(1) and AT(2) receptors. In rodents, two AT(1) receptors have been identified, AT(1A) and AT(1B), whereas in humans a single AT(1) receptor exists. Recently, a number of transgenic animal models have been generated which overexpress or lack functional angiotensin II receptor subtypes. This review focuses on the physiological significance of angiotensin II receptor subtype diversity in the cardiovascular system. In the mouse, AT(1A) receptors are the major regulators of cardiovascular homeostasis by determining vascular tone and natriuresis. In addition, AT(1A) receptors mediate growth-stimulating signals in vascular and cardiac myocytes. AT(1B) receptors participate in blood pressure regulation, and their functions become apparent when the AT(1A) receptor gene is deleted. Deletion of the mouse gene for the AT(2) receptor subtype led to hypersensitivity to pressor and antinatriuretic effects of angiotensin II in vivo, suggesting that the AT(2) receptor subtype counteracts some of the biological effects of AT(1) receptor signalling. 相似文献
70.
Margrete Solheim Mari C Brekke Lars G Snipen Rob JL Willems Ingolf F Nes Dag A Brede 《BMC microbiology》2011,11(1):3