全文获取类型
收费全文 | 248篇 |
免费 | 25篇 |
出版年
2021年 | 2篇 |
2017年 | 4篇 |
2015年 | 9篇 |
2014年 | 5篇 |
2013年 | 5篇 |
2012年 | 10篇 |
2011年 | 19篇 |
2010年 | 11篇 |
2009年 | 8篇 |
2008年 | 4篇 |
2007年 | 12篇 |
2006年 | 6篇 |
2005年 | 14篇 |
2004年 | 9篇 |
2003年 | 9篇 |
2002年 | 11篇 |
2001年 | 9篇 |
2000年 | 5篇 |
1999年 | 6篇 |
1998年 | 3篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 4篇 |
1992年 | 4篇 |
1990年 | 5篇 |
1989年 | 7篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 6篇 |
1985年 | 8篇 |
1984年 | 2篇 |
1983年 | 5篇 |
1982年 | 8篇 |
1981年 | 5篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1972年 | 3篇 |
1971年 | 3篇 |
1970年 | 1篇 |
1969年 | 2篇 |
1968年 | 3篇 |
1967年 | 3篇 |
1966年 | 2篇 |
排序方式: 共有273条查询结果,搜索用时 15 毫秒
71.
Effect of diabetes on acid and neutral triacylglycerol lipase and on lipoprotein lipase activities in isolated myocardial cells from rat heart. 总被引:2,自引:1,他引:1
下载免费PDF全文
![点击此处可从《The Biochemical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
A neutral triacylglycerol lipase activity that is separate and distinct from lipoprotein lipase (LPL) could be measured in homogenates of myocardial cells if protamine sulphate and high concentrations of albumin were included in the assay. This neutral lipase was predominantly particulate, with the highest relative specific activity in microsomal subcellular fractions. The induction of diabetes by the administration of streptozotocin to rats resulted in a decrease in LPL activity in myocyte homogenates and in particulate subcellular fractions, but the percentage of cellular LPL activity that was released during incubation of myocytes with heparin was normal. In contrast, neutral lipase activity was increased in diabetic myocyte homogenates and microsomal fractions. Acid triacylglycerol lipase activity was not changed in diabetic myocytes. The decrease in LPL in myocytes owing to diabetes may result in the decreased functional LPL activity at the capillary endothelium of the diabetic heart. 相似文献
72.
Seventy-three patients were studied after ingesting a liquid glucose meal, tagged with 113Indium. Nineteen of these patients were awaiting surgery for their duodenal ulcer, while 54 were studied postoperatively, 25 of whom experienced troublesome postprandial (dumping) symptoms in their daily lives. The radioactive marker emptied significantly faster in the symptomatic patients than in the symptomfree, pre and post-operative groups (initial emptying rate 3.45 ± 0.23, compared with 1.16 ± 0.19 and 1.27 ± 0.15% fall in counts/min respectively; p < 0.01). Initial (20 min) rises in the plasma concentrations of neurotensin-like immunoreactivity measured during the test correlated significantly with the rate of gastric emptying in all patients, being greatest in patients with dumping symptoms. Physiological concentrations of neurotensin have been shown to delay gastric emptying. The excessive rise in plasma neurotensin-like immunoreactivity in patients with dumping symptoms, presumably occuring as a result of the rapid passage of nutrients to the neurotensin-rich ileum, may possibly have a compensatory role in slowing further emptying from the stomach. 相似文献
73.
Specific uptake (S.U.) of α-aminoisobutyric acid ([1-14C]AIB), a non-metabolizable neutral amino acid analog, by dwarf bush bean plants (Phaseolus vulgaris cv Top Crop) demonstrated wide differences in active transport between various plant organs. The kinetic and timed uptake data reported were expressed as S.U. because this corrects for the diffusion of AIB which is part of the total AIB uptake process. Roots accumulated AIB to concentrations up to 18 times and leaf disks to twice those of the incubation medium. Stem tissue showed very little uptake, if any, that could not be accounted for by simple diffusion or water free space. Although initial rate kinetic studies demonstrated the presence of a normal transport system, timed uptake studies revealed greatly decreased transport by etiolated plants, suggesting a relationship between active transport and the lack of photosynthate. The reproducibility of the AIB uptake pattern by mature roots strongly supports the concept that the transport of neutral amino acids is biphasic and suggested one or more carrier systems are inducible by either low intracellular concentrations or repressed by high intracellular concentrations of the amino acid. 相似文献
74.
75.
76.
A R Severson 《Hormones et métabolisme》1978,10(3):256-260
Addition of dibutyryl cyclic AMP or parathyroid hormone to bone organ cultures markedly increased the incorporation of 3H-glucosamine into non-dialyzable macromolecules. Other cyclic nucleotides or their dibutyryl derivatives did not stimulate glucosamine incorporation. DEAE-cellulose chromatography of the papain-digested calvaria and culture medium resolved the labeled material into four peaks. A four-fold increase in radioactivity was observed in peak III. Previous studies of peak III have identified the labeled material as hyaluronic acid. The results suggest that the parathyroid hormone stimulated increase in glucosamine incorporation is mediated via the adenylate cyclase-cyclic AMP system, and that the increased amount of radioactivity is due to an increased amount of hyaluronic acid. Turnover studied of the labeled material suggest that the release of proteoglycans into the culture medium is not inhibited in the cultures treated with dibutyryl cyclic AMP. The role of hyaluronate in this experimental system remains to be elucidated. 相似文献
77.
Oswaldo Keith Okamoto Ana Carolina SR Carvalho Luciana C Marti Ricardo Z Vêncio Carlos A Moreira-Filho 《Cancer cell international》2007,7(1):11
Background
Uncovering the molecular mechanism underlying expansion of hematopoietic stem and progenitor cells is critical to extend current therapeutic applications and to understand how its deregulation relates to leukemia. The characterization of genes commonly relevant to stem/progenitor cell expansion and tumor development should facilitate the identification of novel therapeutic targets in cancer. 相似文献78.
Hafstad AD Solevåg GH Severson DL Larsen TS Aasum E 《American journal of physiology. Heart and circulatory physiology》2006,290(5):H1763-H1769
Diabetic (db/db) mice provide an animal model of Type 2 diabetes characterized by marked in vivo insulin resistance. The effect of insulin on myocardial metabolism has not been fully elucidated in this diabetic model. In the present study we tested the hypothesis that the metabolic response to insulin in db/db hearts will be diminished due to cardiac insulin resistance. Insulin-induced changes in glucose oxidation (GLUox) and fatty acid (FA) oxidation (FAox) were measured in isolated hearts from control and diabetic mice, perfused with both low as well as high concentration of glucose and FA: 10 mM glucose/0.5 mM palmitate and 28 mM glucose/1.1 mM palmitate. Both in the absence and presence of insulin, diabetic hearts showed decreased rates of GLUox and elevated rates of FAox. However, the insulin-induced increment in GLUox, as well as the insulin-induced decrement in FAox, was similar or even more pronounced in diabetic that in control hearts. During elevated FA and glucose supply, however, the effect of insulin was blunted in db/db hearts with respect to both FAox and GLUox. Finally, insulin-stimulated deoxyglucose uptake was markedly reduced in isolated cardiomyocytes from db/db mice, whereas glucose uptake in isolated perfused db/db hearts was clearly responsive to insulin. These results show that, despite reduced insulin-stimulated glucose uptake in isolated cardiomyocytes, isolated perfused db/db hearts are responsive to metabolic actions of insulin. These results should advocate the use of insulin therapy (glucose-insulin-potassium) in diabetic patients undergoing cardiac surgery or during reperfusion after an ischemic insult. 相似文献
79.
Junctional Adhesion Molecule A Interacts with Afadin and PDZ-GEF2 to Activate Rap1A, Regulate β1 Integrin Levels, and Enhance Cell Migration
下载免费PDF全文
![点击此处可从《Molecular biology of the cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Eric A. Severson Winston Y. Lee Christopher T. Capaldo Asma Nusrat Charles A. Parkos 《Molecular biology of the cell》2009,20(7):1916-1925
Junctional adhesion molecule-A (JAM-A) is a transmembrane tight junction protein that has been shown to regulate barrier function and cell migration through incompletely understood mechanisms. We have previously demonstrated that JAM-A regulates cell migration by dimerization of the membrane-distal immunoglobulin-like loop and a C-terminal postsynaptic density 95/disc-large/zona occludens (PDZ) binding motif. Disruption of dimerization resulted in decreased epithelial cell migration secondary to diminished levels of β1 integrin and active Rap1. Here, we report that JAM-A is physically and functionally associated with the PDZ domain-containing molecules Afadin and PDZ-guanine nucleotide exchange factor (GEF) 2, but not zonula occludens (ZO)-1, in epithelial cells, and these interactions mediate outside-in signaling events. Both Afadin and PDZ-GEF2 colocalized and coimmunoprecipitated with JAM-A. Furthermore, association of PDZ-GEF2 with Afadin was dependent on the expression of JAM-A. Loss of JAM-A, Afadin, or PDZ-GEF2, but not ZO-1 or PDZ-GEF1, similarly decreased cellular levels of activated Rap1, β1 integrin protein, and epithelial cell migration. The functional effects observed were secondary to decreased levels of Rap1A because knockdown of Rap1A, but not Rap1B, resulted in decreased β1 integrin levels and reduced cell migration. These findings suggest that JAM-A dimerization facilitates formation of a complex with Afadin and PDZ-GEF2 that activates Rap1A, which regulates β1 integrin levels and cell migration. 相似文献
80.
IL2RA Genetic Heterogeneity in Multiple Sclerosis and Type 1 Diabetes Susceptibility and Soluble Interleukin-2 Receptor Production
下载免费PDF全文
![点击此处可从《PLoS genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Lisa M. Maier Christopher E. Lowe Jason Cooper Kate Downes David E. Anderson Christopher Severson Pamela M. Clark Brian Healy Neil Walker Cristin Aubin Jorge R. Oksenberg Stephen L. Hauser Alistair Compston Stephen Sawcer The International Multiple Sclerosis Genetics Consortium Philip L. De Jager Linda S. Wicker John A. Todd David A. Hafler 《PLoS genetics》2009,5(1)
Multiple sclerosis (MS) and type 1 diabetes (T1D) are organ-specific autoimmune disorders with significant heritability, part of which is conferred by shared alleles. For decades, the Human Leukocyte Antigen (HLA) complex was the only known susceptibility locus for both T1D and MS, but loci outside the HLA complex harboring risk alleles have been discovered and fully replicated. A genome-wide association scan for MS risk genes and candidate gene association studies have previously described the IL2RA gene region as a shared autoimmune locus. In order to investigate whether autoimmunity risk at IL2RA was due to distinct or shared alleles, we performed a genetic association study of three IL2RA variants in a DNA collection of up to 9,407 healthy controls, 2,420 MS, and 6,425 T1D subjects as well as 1,303 MS parent/child trios. Here, we report “allelic heterogeneity” at the IL2RA region between MS and T1D. We observe an allele associated with susceptibility to one disease and risk to the other, an allele that confers susceptibility to both diseases, and an allele that may only confer susceptibility to T1D. In addition, we tested the levels of soluble interleukin-2 receptor (sIL-2RA) in the serum from up to 69 healthy control subjects, 285 MS, and 1,317 T1D subjects. We demonstrate that multiple variants independently correlate with sIL-2RA levels. 相似文献