全文获取类型
收费全文 | 513篇 |
免费 | 43篇 |
出版年
2021年 | 7篇 |
2019年 | 2篇 |
2018年 | 4篇 |
2017年 | 2篇 |
2016年 | 11篇 |
2015年 | 21篇 |
2014年 | 14篇 |
2013年 | 25篇 |
2012年 | 41篇 |
2011年 | 29篇 |
2010年 | 22篇 |
2009年 | 30篇 |
2008年 | 38篇 |
2007年 | 24篇 |
2006年 | 30篇 |
2005年 | 33篇 |
2004年 | 25篇 |
2003年 | 27篇 |
2002年 | 33篇 |
2001年 | 8篇 |
2000年 | 6篇 |
1999年 | 9篇 |
1998年 | 11篇 |
1997年 | 4篇 |
1996年 | 8篇 |
1995年 | 9篇 |
1994年 | 11篇 |
1993年 | 3篇 |
1992年 | 8篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 9篇 |
1988年 | 5篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1985年 | 7篇 |
1984年 | 3篇 |
1983年 | 5篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1978年 | 4篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1966年 | 1篇 |
1960年 | 1篇 |
1936年 | 1篇 |
排序方式: 共有556条查询结果,搜索用时 15 毫秒
1.
2.
Bruno Mhul Michle Aubery Hans-Georg Mannherz Patrice Codogno 《Journal of cellular biochemistry》1993,52(3):266-274
The myoblast cell surface activity of ecto-5′-nucleotidase was stimulated by a laminin substrate, whereas fibronectin and gelatin did not increase the AMPase activity of ecto-5′-nucleotidase. This increase was related to a higher expression of ecto-5′-nucleotidase on the surface of cells seeded on a laminin substrate, but without the mobilization of an intracellular pool of enzyme. Furthermore, laminin and its fragments E′1 and E8 modified the AMPase activity of the ecto-5′-nucleotidase purified from chicken striated muscle and reconstituted in liposomes. Over the range of concentrations used, intact laminin and its fragment E8, consisting of the distal half of the long arm, stimulated the AMPase activity of ecto-5′-nucleotidase. By contrast, the large fragment derived from the short arms, designated E′1, inhibited the AMPase activity. Furthermore, the monoclonal anti-ecto-5′-nucleotidase antibody, CG37, abolished the stimulatory effect of fragment E8 on the AMPase activity of ecto-5′-nucleotidase but did not reverse the inhibitory effect of fragment E′1. In conclusion, laminin stimulates the AMPase activity of ecto-5′-nucleotidase by two mechanisms: inducing the expression of ecto-5′-nucleotidase to the cell surface and direct modulation of the enzymatic activity. 相似文献
3.
Obesity-associated diabetes (“diabesity”) in mouse strains is characterized by severe insulin resistance, hyperglycaemia and progressive failure, and loss of beta cells. This condition is observed in inbred obese mouse strains such as the New Zealand Obese (NZO/HlLt and NZO/HlBomDife) or the TALLYHO/JngJ mouse. In lean strains such as C57BLKS/J, BTBR T+tf/J or DBA/2 J carrying diabetes susceptibility genes (“diabetes susceptible” background), it can be induced by introgression of the obesity-causing mutations Lep (ob) or Lepr (db). Outcross populations of these models have been employed in the genome-wide search for mouse diabetes genes, and have led to positional cloning of the strong candidates Pctp, Tbc1d1, Zfp69, and Ifi202b (NZO-derived obesity) and Sorcs1, Lisch-like, Tomosyn-2, App, Tsc2, and Ube2l6 (obesity caused by the ob or db mutation). Some of these genes have been shown to play a role in the regulation of the human glucose or lipid metabolism. Thus, dissection of the genetic basis of obesity and diabetes in mouse models can identify regulatory mechanisms that are relevant for the human disease. 相似文献
4.
5.
Dennis C. Koch Thomas H. Schmidt Hans-Georg Sahl Ulrich Kubitscheck Christian Kandt 《生物化学与生物物理学报:生物膜》2014
Representing a physiological “Achilles' heel”, the cell wall precursor lipid II (LII) is a prime target for various classes of antibiotics. Over the years LII-binding agents have been recognized as promising candidates and templates in the search for new antibacterial compounds to complement or replace existing drugs. To elucidate the molecular structural basis underlying LII functional mechanism and to better understand if and how lantibiotic binding alters the molecular behavior of LII, we performed molecular dynamics (MD) simulations of phospholipid membrane-embedded LII in the absence and presence of the LII-binding lantibiotic nisin. In a series of 2 × 4 independent, unbiased 100 ns MD simulations we sampled the conformational dynamics of nine LII as well as nine LII–nisin complexes embedded in an aqueous 150 mM NaCl/POPC phospholipid membrane environment. We found that nisin binding to LII induces a reduction of LII mobility and flexibility, an outward shift of the LII pentapeptide, an inward movement of the LII disaccharide section, and an overall deeper insertion of the LII tail group into the membrane. The latter effect might indicate an initial step in adopting a stabilizing, scaffold-like structure in the process of nisin-induced membrane leakage. At the same time nisin conformation and LII interaction remain similar to the 1WCO LII–nisin NMR solution structure. 相似文献
6.
7.
Influence of the staphylococcinlike peptide Pep 5 on membrane potential of bacterial cells and cytoplasmic membrane vesicles. 总被引:15,自引:4,他引:11 下载免费PDF全文
H G Sahl 《Journal of bacteriology》1985,162(2):833-836
The staphylococcinlike peptide Pep 5 rapidly abolished the membrane potential of bacterial cells; active transport of amino acids by cytoplasmic membrane vesicles was inhibited and preaccumulated amino acids were released upon the addition of Pep 5. Artificial asolectin vesicles were not impaired by the peptide. It is concluded that the cytoplasmic membrane is the primary target of Pep 5. 相似文献
8.
Michael K Boettger Johannes Leuchtweis Diana Kümmel Mieczyslaw Gajda Rolf Br?uer Hans-Georg Schaible 《Arthritis research & therapy》2010,12(4):R140
Introduction
Interleukin-6 (IL-6) is a key player in systemic arthritis, involved in inflammation and joint destruction. IL-6 signalling has also been revealed in nerve cells. Recently, IL-6 and in particular IL-6 together with its soluble IL-6 receptor (sIL-6R) were shown to induce a long-lasting robust sensitization of joint nociceptors for mechanical stimuli which was difficult to reverse, suggesting that IL-6 signalling plays a significant role in the generation and maintenance of arthritic pain. Here we tested in a preclinical model of arthritis, antigen-induced arthritis (AIA) in the rat, whether systemic or local neutralization of IL-6/sIL-6R complexes with soluble glycoprotein 130 (sgp130) alters arthritic pain and how sgp130 influences the inflammatory process in AIA. 相似文献9.
Induction of autolysis of staphylococci by the basic peptide antibiotics Pep 5 and nisin and their influence on the activity of autolytic enzymes 总被引:12,自引:0,他引:12
Pep 5 and nisin are cationic bactericidal peptides which were shown to induce autolysis in Staphylococcus cohnii 22. In contrast to nisin, Pep 5 induced lysis could be stimulated in the presence of glucose. Addition of lipoteichoic acids (LTA) (d-alanine:phosphorus=0.475:1) inhibited all effects of Pep 5 on susceptible cells in a molar ratio LTA:Pep 5 of 10:1. Treatment of S. cohnii 22 with Pep 5 or nisin for 20 min and subsequent washing with 2.5 M NaCl released autolysin activity. Crude preparations of the hydrolyzing enzymes produced free amino groups as well as polysaccharide fragments from the murein backbone, suggesting the presence of a muramidase or glucosamidase, and endopeptidase or amidase. Both enzyme activities were inhibited by lipoteichoic acid; they could be fully reactivated by addition of Pep 5 in sufficient concentrations. The velocity of hydrolysis was not influenced by nisin, whereas it was doubled in presence of Pep 5. The results are discussed in view of a possible mechanism of induction of lysis by Pep 5 and nisin.Abbreviations A.U.
arbitrary unit
- CCCP
carbonylcyanide-m-chlorophenyl hydrazone
- DNase
deoxyribonuclease
- CYG
casein yeast extract glucose
- IT
initial turbidity
- LTA
lipoteichoic acid
- RNase
ribonuclease
- TSB
Tryptone Soy Broth 相似文献
10.
Voltage-dependent depolarization of bacterial membranes and artificial lipid bilayers by the peptide antibiotic nisin 总被引:24,自引:0,他引:24
The peptide antibiotic nisin is shown to disrupt valinomycin-induced potassium diffusion potentials imposed on intact cells of Staphylococcus cohnii 22. Membrane depolarization occurred rapidly at high diffusion potentials while at low potentials nisin-induced depolarization was slower suggesting that nisin requires a membrane potential for activity. This assumption was proven in experiments with planar lipid bilayers (black lipid membranes). Macroscopic conductivity measurements indicated a voltage-dependent action of nisin. The potential must have a trans-negative orientation with respect to the addition of nisin (added to the cis-side) and a sufficient magnitude (ca. -100 mV). With intact cells the threshold potential was lower (-50 to -80 mV at pH 7.5 and below -50 mV at pH 5.5). Single channel recordings resolved transient multistate pores, strongly resembling those introduced by melittin into artificial bilayers. The pores had diameters in the range of 0.2–1 nm, and lifetimes of few to several hundred milliseconds. The results indicate that nisin has to be regarded as a membrane-depolarizing agent which acts in a voltage-dependent fashion.Abbreviations BLM
Black lipid membranes
- CCCP
carbonyl cyanide m-chlorophenylhydrazone
- DOPC
dioleoyl phosphatidylcholine
- PS
phosphatidylserine
- TPP+
tetraphenylphosphonium cation 相似文献