全文获取类型
收费全文 | 307篇 |
免费 | 39篇 |
出版年
2021年 | 5篇 |
2017年 | 3篇 |
2015年 | 12篇 |
2014年 | 5篇 |
2013年 | 12篇 |
2012年 | 7篇 |
2011年 | 12篇 |
2010年 | 13篇 |
2009年 | 5篇 |
2008年 | 5篇 |
2007年 | 12篇 |
2006年 | 16篇 |
2005年 | 8篇 |
2004年 | 5篇 |
2003年 | 9篇 |
2002年 | 5篇 |
2001年 | 5篇 |
2000年 | 6篇 |
1999年 | 3篇 |
1998年 | 5篇 |
1997年 | 6篇 |
1996年 | 5篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 6篇 |
1991年 | 7篇 |
1990年 | 6篇 |
1989年 | 4篇 |
1988年 | 6篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 6篇 |
1983年 | 8篇 |
1982年 | 11篇 |
1981年 | 3篇 |
1974年 | 4篇 |
1972年 | 3篇 |
1970年 | 5篇 |
1968年 | 4篇 |
1966年 | 3篇 |
1964年 | 3篇 |
1963年 | 4篇 |
1962年 | 4篇 |
1960年 | 3篇 |
1950年 | 3篇 |
1944年 | 3篇 |
1937年 | 7篇 |
1935年 | 3篇 |
1924年 | 2篇 |
1923年 | 2篇 |
排序方式: 共有346条查询结果,搜索用时 515 毫秒
191.
192.
Andrew J. Streets Andrew J. Needham Sharonjit K. Gill Albert C. M. Ong 《Molecular biology of the cell》2010,21(22):3853-3865
PKD2 is mutated in 15% of patients with autosomal dominant polycystic kidney disease. The PKD2 protein, polycystin-2 or TRPP2, is a nonselective Ca2+-permeable cation channel that has been shown to function at several locations, including primary cilia, basolateral membrane, and at the endoplasmic reticulum (ER). Nevertheless, the factors that regulate the channel activity of polycystin-2 are not well understood. Polycystin-2 has been shown previously to be regulated by phosphorylation at two serine residues (Ser812 and Ser76) with distinct functional consequences. Here, we report the identification of a previously unrecognized phosphorylation site within the polycystin-2 C terminus (Ser801), and we demonstrate that it is phosphorylated by protein kinase D. Phosphorylation at this site was significantly increased in response to serum and epidermal growth factor stimulation. In nonciliated Madin-Darby canine kidney I cells, inducible expression of polycystin-2 inhibited cell proliferation compared with wild-type cells. Mutagenesis at Ser801 abolished these effects and reduced ATP-stimulated Ca2+ release from ER stores. Finally, we show that a pathogenic mutation (S804N) within the consensus kinase recognition sequence abolished Ser801 phosphorylation. These results suggest that growth factor-stimulated, protein kinase D-mediated phosphorylation of polycystin-2 is essential for its ER channel function and links extracellular stimuli to its effects on cell growth and intracellular calcium regulation. 相似文献
193.
The complexity of human gait patterns has become a topic of major interest in motor control and biomechanics. Range of motion is still the preferred method to quantify movement impairment, however, within these traditional linear measures, the inter-segmental coordination and movement variability is normally ignored. A dynamical systems approach using vector coding and circular statistics provides non-linear techniques to quantify coordination and variability. This study provides comprehensive vector coding and circular statistics calculations. Additionally, pelvis–lumbar coordination and coordination variability data obtained from ten healthy young male participants during five walking trials using an optoelectronic system is provided. This novel data can form the baseline information for future studies in this area of research. Finally, a new illustration to present coordination and coordination variability information of gait kinematics, combining the output from the modified vector coding technique with traditional time-series segmental angle data is presented. This technique, when applied to single patients can be beneficial to assess the effect of an intervention on the patient-specific inter-segmental coordination pattern with implications to the clinical setting. 相似文献
194.
M. J. Silva J. A. Reidy K. Kato J. L. Preau JR L. L. Needham A. M. Calafat 《Biomarkers》2013,18(2):133-144
Di-isodecyl phthalate (DiDP), primarily used as a plasticiser, is a mixture of isomers with predominantly ten-carbon branched side chains. Assessment of DiDP exposure has not been conducted before because adequate biomarkers were lacking. In 129 adult volunteers with no known exposure to DiDP, the urinary concentrations of three oxidative metabolites of DiDP: monocarboxyisononyl phthalate (MCiNP), monooxoisodecyl phthalate (MOiDP) and monohydroxyisodecyl phthalate (MHiDP), previously identified in DiDP-dosed rats, were estimated by solid-phase extraction coupled to high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) using the respective oxidative metabolites of di(2-ethylhexyl)phthalate since authentic standards of the DiDP oxidative metabolites were unavailable. Interestingly, the hydrolytic monoester of DiDP, monoisodecyl phthalate (MiDP), was not detected in any of the samples, while MCiNP, MHiDP and MOiDP were detected in 98%, 96% and 85%, respectively, of the samples tested. MCiNP was excreted predominantly in its free form, whereas MOiDP was excreted as its glucuronide. MCiNP, MHiDP and MOiDP eluted as clusters of multiple peaks from the HPLC column probably due to the presence of numerous structurally similar isomers present in commercial DiDP formulations. The urinary concentrations of these oxidative metabolites correlated significantly (p<0.0001) with each other, thus confirming a common precursor. The urinary concentrations of these DiDP oxidative metabolites also correlated significantly (p<0.0001) with oxidative metabolites of di-isononyl phthalate (DiNP) suggesting the potential presence of DiNP isomers in commercial DiDP or simultaneous use of DiDP and DiNP in consumer products. The concentrations presented are semiquantitative estimates and should be interpreted cautiously. Nevertheless, the higher frequency of detection and higher urinary concentrations of MCiNP, MHiDP and MOiDP than of MiDP suggest that these oxidative metabolites are better biomarkers for DiDP exposure assessment than MiDP. These data also suggest that unless oxidative metabolites are measured, the prevalence of exposure to DiDP will probably be underestimated. 相似文献
195.
Quinidine and melittin both decrease the fluidity of liver plasma membranes and both inhibit hormone-stimulated adenylate cyclase activity 总被引:1,自引:0,他引:1
Increasing concentrations of either quinidine or melittin gave a dose-dependent inhibition of both the glucagon- and fluoride-stimulated activities of adenylate cyclase in the liver plasma membranes. At similar concentrations these agents increased the order of liver plasma membranes as detected by a fatty acid ESR probe, doxyl stearic acid. This increase in bilayer order (decrease in 'fluidity') is suggested to explain the inhibitory action of quinidine on adenylate cyclase activity but only in part contributes to the inhibitory action of melittin on adenylate cyclase. Arrhenius plots of fluoride-stimulated activity became non-linear in the presence of either quinidine or melittin, with a single well-defined break occurring at around 12 degrees C in each instance. Arrhenius plots of the glucagon-stimulated activity also exhibited such a novel break at around 12 degrees C when either quinidine or melittin were present as well as exhibiting a break at around 28 degrees C, as was seen in the absence of these ligands. The fatty acid spin probe inserted into liver plasma membranes detected a novel lipid phase separation occurring at around 12 degrees C when either quinidine or melittin was present and showed that the lipid phase separation occurring at around 28 degrees C in native membranes was apparently unaffected by these ligands. 相似文献
196.
197.
Fred. Needham 《BMJ (Clinical research ed.)》1888,1(1420):614-615
198.
199.
200.