全文获取类型
收费全文 | 786篇 |
免费 | 61篇 |
出版年
2021年 | 11篇 |
2020年 | 4篇 |
2019年 | 11篇 |
2018年 | 7篇 |
2017年 | 8篇 |
2016年 | 12篇 |
2015年 | 31篇 |
2014年 | 18篇 |
2013年 | 33篇 |
2012年 | 54篇 |
2011年 | 46篇 |
2010年 | 35篇 |
2009年 | 41篇 |
2008年 | 46篇 |
2007年 | 45篇 |
2006年 | 46篇 |
2005年 | 52篇 |
2004年 | 50篇 |
2003年 | 49篇 |
2002年 | 34篇 |
2001年 | 11篇 |
2000年 | 10篇 |
1999年 | 14篇 |
1998年 | 8篇 |
1997年 | 9篇 |
1996年 | 9篇 |
1995年 | 9篇 |
1994年 | 10篇 |
1993年 | 11篇 |
1992年 | 6篇 |
1991年 | 5篇 |
1990年 | 5篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1985年 | 7篇 |
1984年 | 8篇 |
1983年 | 6篇 |
1982年 | 8篇 |
1981年 | 8篇 |
1980年 | 13篇 |
1979年 | 5篇 |
1978年 | 4篇 |
1977年 | 4篇 |
1976年 | 5篇 |
1975年 | 5篇 |
1974年 | 4篇 |
1973年 | 5篇 |
1971年 | 3篇 |
排序方式: 共有847条查询结果,搜索用时 15 毫秒
161.
Acknowledgments
Acknowledgements 相似文献162.
Wolfson M Budovsky A Tacutu R Fraifeld V 《The international journal of biochemistry & cell biology》2009,41(3):516-520
The established human age-related disease proteins (ARDPs) and longevity-associated proteins (LAPs) together with their first-order interacting partners form scale-free networks which significantly overlap. About half of the common proteins are involved in signal transduction. These proteins are strongly interconnected and in turn form a common signaling network which comprises over 40% of all hubs (proteins with multiple interactions) in the human interactome. Along with the insulin pathway, the common signaling network is remarkably enriched with the focal adhesion and adherens junction proteins whose relation to the control of lifespan is yet to be fully addressed. The examples of such candidate proteins include several hubs, focal adhesion kinase PTK2 and the extracellular proteins fibronectin FN1, paxillin PXN, and vinculin VCL. The results of the network-based analysis highlight the potential importance of these pathways, especially hubs, in linking the human longevity and age-related diseases. 相似文献
163.
Rodríguez-Manzaneque JC Carpizo D Plaza-Calonge Mdel C Torres-Collado AX Thai SN Simons M Horowitz A Iruela-Arispe ML 《The international journal of biochemistry & cell biology》2009,41(4):800-810
Syndecan-4 is a membrane-bound heparan sulfate proteoglycan that participates in cell-cell and cell-matrix interactions and modulates adhesion and migration of many cell types. Through its extracellular domain, syndecan-4 cooperates with adhesion molecules and binds matrix components relevant for cell migration. Importantly, syndecan-4 is a substrate of extracellular proteases, however the biological significance of this cleavage has not been elucidated. Here, we show that the secreted metalloprotease ADAMTS1, involved in angiogenesis and inflammatory processes, cleaves the ectodomain of syndecan-4. We further showed that this cleavage results in altered distribution of cytoskeleton components, functional loss of adhesion, and gain of migratory capacities. Using syndecan-4 null cells, we observed that ADAMTS1 proteolytic action mimics the outcome of genetic deletion of this proteoglycan with regards to focal adhesion. Our findings suggest that the shedding of syndecan-4 by ADAMTS1 disrupts cell adhesion and promotes cell migration. 相似文献
164.
Rien van Haperen Hannelore Samyn Teus van Gent Adri J. Zonneveld Matthijs Moerland Frank Grosveld Hans Jansen Geesje M. Dallinga-Thie Arie van Tol Rini de Crom 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2009,1791(10):1031-1036
Objective
Elevated plasma phospholipid transfer protein (PLTP) expression may increase atherosclerosis in mice by reducing plasma HDL and increasing hepatic VLDL secretion. Hepatic lipase (HL) is a lipolytic enzyme involved in several aspects of the same pathways of lipoprotein metabolism. We investigated whether the effects of elevated PLTP activity are compromised by HL deficiency.Methods and results
HL deficient mice were crossbred with PLTP transgenic (PLTPtg) mice and studied in the fasted state. Plasma triglycerides were decreased in HL deficiency, explained by reduced hepatic triglyceride secretion. In PLTPtg mice, a redistribution of HL activity between plasma and tissue was evident and plasma triglycerides were also decreased. HL deficiency mitigated or even abolished the stimulatory effect of elevated PLTP activity on hepatic triglyceride secretion. HL deficiency had a modest incremental effect on plasma HDL, which remained present in PLTP transgenic/HL−/− mice, thereby partially compensating the decrease in HDL caused by elevation of PLTP activity. HDL decay experiments showed that the fractional turnover rate of HDL cholesteryl esters was delayed in HL deficient mice, increased in PLTPtg mice and intermediate in PLTPtg mice in an HL−/− background.Conclusions
HL affects hepatic VLDL. Elevated PLTP activity lowers plasma HDL-cholesterol by stimulating the plasma turnover and hepatic uptake of HDL cholesteryl esters. HL is not required for the increase in hepatic triglyceride secretion or for the lowering of HDL-cholesterol induced by PLTP overexpression. 相似文献165.
Hannelore Samyn Matthijs Moerland Teus van Gent Rien van Haperen Arie van Tol Rini de Crom 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2009,1791(8):790-796
Phospholipid transfer protein (PLTP) is associated with HDL particles in plasma, where it transfers phospholipids between lipoproteins and remodels HDL particles. Tangier disease patients, with a mutated ABCA1 transporter, have extremely low plasma HDL concentration and reduced PLTP activity levels, a phenotype that is also observed in mice lacking ABCA1. We investigated whether low HDL levels and low PLTP activity are mechanistically related. Firstly, we studied PLTP expression and distribution among lipoproteins in mice lacking ABCA1 (ABCA1−/−). Parallel to the strong reduction in PLTP activity in plasma of ABCA1−/− mice, decreased PLTP protein levels were observed. Neither PLTP synthesis in liver or macrophages nor the ability of the macrophages to secrete PLTP were impaired in ABCA1−/− mice. However, the PLTP activity level in the medium of cultured macrophages was determined by HDL levels in the medium. PLTP was associated with HDL particles in wild type mice, whereas in ABCA1−/− mice, PLTP was associated with VLDL and LDL particles. Secondly, we treated different mouse models with varying plasma HDL and PLTP levels (wild type, ABCA1−/−, apoE−/− and PLTPtg mice, overexpressing human PLTP) with a synthetic LXR ligand, and investigated the relationship between LXR-mediated PLTP induction and HDL levels in plasma. Plasma PLTP activity in wild type mice was induced 5.6-fold after LXR activation, whereas in ABCA1−/−, apoE−/− and PLTPtg mice, all having reduced HDL levels, induction of PLTP activity was 2.4- , 3.2- and 2.0-fold, respectively. The less pronounced PLTP induction in these mice compared to wild type mice was not caused by a decreased PLTP gene expression in the liver or macrophages. Our findings indicate that the extent of LXR-mediated PLTP induction depends on plasma HDL levels. In conclusion, we demonstrate that ABCA1 deficiency in mice affects plasma PLTP level and distribution through an indirect effect on HDL metabolism. In addition, we show that the extent of LXR-mediated PLTP induction is HDL-dependent. These findings indicate that plasma HDL level is an important regulator of plasma PLTP and might play a role in the stabilization of PLTP in plasma. 相似文献
166.
Yuko Arie Masumi Iketani Ken Takamatsu Yoshio Goshima 《Biochemical and biophysical research communications》2009,379(1):11-3034
Intracellular calcium ions (Ca2+) have an essential role in the regulation of neurite outgrowth, but how outgrowth is controlled remains largely unknown. In this study, we examined how the mechanisms of neurite outgrowth change during development in chick and mouse dorsal root ganglion neurons. 2APB, a potent inhibitor of inositol 1,4,5-trisphosphate (IP3) receptors (IP3R), inhibited neurite outgrowth at early developmental stages, but not at later stages. In contrast, pharmacological inhibition with Ni2+, Cd2+, or dantrolene revealed that ryanodine receptor (RyR)-mediated Ca2+-induced Ca2+ release (CICR) was involved in neurite outgrowth at later stage, but not at early stages. The distribution of IP3R and RyR in growth cones also changed during development. Furthermore, pharmacological inhibition of the Ca2+-calmodulin-dependent phosphatase calcineurin with FK506 reduced neurite outgrowth only at early stages. These data suggest that the calcium signaling that regulates neurite outgrowth may change during development from an IP3R-mediated pathway to a RyR-mediated pathway. 相似文献
167.
Rutters F Nieuwenhuizen AG Lemmens SG Born JM Westerterp-Plantenga MS 《Obesity (Silver Spring, Md.)》2009,17(1):72-77
Obesity results from chronic deregulation of energy balance, which may in part be caused by stress. Our objective was to investigate the effect of acute and psychological stress on food intake, using the eating in the absence of hunger paradigm, in normal and overweight men and women (while taking dietary restraint and disinhibition into account). In 129 subjects (BMI = 24.5 +/- 3.4 kg/m(2) and age = 27.6 +/- 8.8 years), scores were determined on the Three Factor Eating Questionnaire (dietary restraint = 7.2 +/- 4.4; disinhibition = 4.5 +/- 2.6; feeling of hunger = 3.9 +/- 2.6) and State-Trait Anxiety Inventory (trait score = 31.7 +/- 24.2). In a randomized crossover design, the "eating in absence of hunger" protocol was measured as a function of acute stress vs. a control task and of state anxiety scores. Energy intake from sweet foods (708.1 kJ vs. 599.4 kJ, P < 0.03) and total energy intake (965.2 kJ vs. 793.8 kJ, P < 0.01) were significantly higher in the stress condition compared to the control condition. Differences in energy intake between the stress and control condition were a function of increase in state anxiety scores during the stress task (Delta state anxiety scores) (R(2) = 0.05, P < 0.01). This positive relationship was stronger in subjects with high disinhibition scores (R(2) = 0.12, P < 0.05). Differences in state anxiety scores were a function of trait anxiety scores (R(2) = 0.07, P < 0.05). We conclude that acute psychological stress is associated with eating in the absence of hunger, especially in vulnerable individuals characterized by disinhibited eating behavior and sensitivity to chronic stress. 相似文献
168.
Nick Barker Meritxell Huch Pekka Kujala Marc van de Wetering Hugo J. Snippert Johan H. van Es Toshiro Sato Daniel E. Stange Harry Begthel Maaike van den Born Esther Danenberg Stieneke van den Brink Jeroen Korving Arie Abo Peter J. Peters Nick Wright Richard Poulsom Hans Clevers 《Cell Stem Cell》2010,6(1):25-36
169.
Amos Danielli Noga Porat Marcelo Ehrlich Ady Arie 《Journal of visualized experiments : JoVE》2010,(40)
A magnetic modulation biosensing system (MMB) [1,2] rapidly and homogeneously detected biological targets at low concentrations without any washing or separation step. When the IL-8 target was present, a ''sandwich''-based assay attached magnetic beads with IL-8 capture antibody to streptavidin coupled fluorescent protein via the IL-8 target and a biotinylated IL-8 antibody. The magnetic beads are maneuvered into oscillatory motion by applying an alternating magnetic field gradient through two electromagnetic poles. The fluorescent proteins, which are attached to the magnetic beads are condensed into the detection area and their movement in and out of an orthogonal laser beam produces a periodic fluorescent signal that is demodulated using synchronous detection. The magnetic modulation biosensing system was previously used to detect the coding sequences of the non-structural Ibaraki virus protein 3 (NS3) complementary DNA (cDNA) [2]. The techniques that are demonstrated in this work for external manipulation and condensation of particles may be used for other applications, e.g. delivery of magnetically-coupled drugs in-vivo or enhancing the contrast for in-vivo imaging applications.Download video file.(80M, mp4) 相似文献
170.
Havelaar AH van Rosse F Bucura C Toetenel MA Haagsma JA Kurowicka D Heesterbeek JH Speybroeck N Langelaar MF van der Giessen JW Cooke RM Braks MA 《PloS one》2010,5(11):e13965