全文获取类型
收费全文 | 103篇 |
免费 | 22篇 |
专业分类
125篇 |
出版年
2021年 | 3篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 2篇 |
2017年 | 2篇 |
2016年 | 6篇 |
2015年 | 9篇 |
2014年 | 5篇 |
2013年 | 6篇 |
2012年 | 8篇 |
2011年 | 11篇 |
2010年 | 3篇 |
2009年 | 2篇 |
2008年 | 7篇 |
2007年 | 6篇 |
2006年 | 5篇 |
2005年 | 8篇 |
2004年 | 6篇 |
2003年 | 2篇 |
2002年 | 4篇 |
2001年 | 2篇 |
2000年 | 3篇 |
1999年 | 1篇 |
1998年 | 3篇 |
1995年 | 3篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 4篇 |
1986年 | 1篇 |
1983年 | 1篇 |
排序方式: 共有125条查询结果,搜索用时 0 毫秒
21.
Rahnema P Shimoni Y Nygren A 《American journal of physiology. Heart and circulatory physiology》2011,300(1):H326-H334
Hearts from streptozotocin (STZ)-induced diabetic rats have previously been shown to have impaired intercellular electrical coupling, due to reorganization (lateralization) of connexin43 proteins. Due to the resulting reduction in conduction reserve, conduction velocity in diabetic hearts is more sensitive to conditions that reduce cellular excitability or intercellular electrical coupling. Diabetes is a known risk factor for cardiac ischemia, a condition associated with both reduced cellular excitability and reduced intercellular coupling. Activation of Ca(2+)-independent phospholipase A(2) (iPLA(2)) is known to be part of the response to acute ischemia and may contribute to the intercellular uncoupling by causing increased levels of arachidonic acid and lysophosphatidyl choline. Normally perfused diabetic hearts are known to exhibit increased iPLA(2) activity and may thus be particularly sensitive to further activation of these enzymes. In this study, we used voltage-sensitive dye mapping to assess changes in conduction velocity in response to acute global ischemia in Langendorff-perfused STZ-induced diabetic hearts. Conduction slowing in response to ischemia was significantly larger in STZ-induced diabetic hearts compared with healthy controls. Similarly, slowing of conduction velocity in response to acidosis was also more pronounced in STZ-induced diabetic hearts. Inhibition of iPLA(2) activity using bromoenol lactone (BEL; 10 μM) had no effect on the response to ischemia in healthy control hearts. However, in STZ-induced diabetic hearts, BEL significantly reduced the amount of conduction slowing observed beginning 5 min after the onset of ischemia. BEL treatment also significantly increased the time to onset of sustained arrhythmias in STZ-induced diabetic hearts but had no effect on the time to arrhythmia in healthy control hearts. Thus, our results suggest that iPLA(2) activation in response to acute ischemia in STZ-induced diabetic hearts is more pronounced than in control hearts and that this response is a significant contributor to arrhythmogenic conduction slowing. 相似文献
22.
23.
Viktoria Stelzhammer Bob Amess Daniel Martins‐de‐Souza Yishai Levin Susan E. Ozanne Malgorzata S. Martin‐Gronert Sebastian Urday Sabine Bahn Paul C. Guest 《Proteomics》2012,12(22):3386-3392
Studies of neuronal, endocrine, and metabolic disorders would be facilitated by characterization of the hypothalamus proteome. Protein extracts prepared from 16 whole rat hypothalami were measured by data‐independent label‐free nano LC‐MS/MS. Peptide features were detected, aligned, and searched against a rat Swiss‐Prot database using ProteinLynx Global Server v.2.5. The final combined dataset comprised 21 455 peptides, corresponding to 622 unique proteins, each identified by a minimum of two distinct peptides. The majority of the proteins (69%) were cytosolic, and 16% were membrane proteins. Important proteins involved in neurological and synaptic function were identified including several members of the Ras‐related protein family and proteins involved in glutamate biosynthesis. 相似文献
24.
Shimoni Y Liu XF 《American journal of physiology. Heart and circulatory physiology》2003,284(4):H1168-H1181
Transient and sustained K(+) currents were measured in isolated rat ventricular myocytes obtained from control, steptozotocin-induced (Type 1) diabetic, and hypothyroid rats. Both currents, attenuated by the endocrine abnormalities, were significantly augmented by in vitro incubation (>6 h) with the angiotensin-converting enzyme inhibitor quinapril or the angiotensin II (ANG II) receptor blocker saralasin. Western blots indicated a parallel increase in Kv4.2 and Kv1.2, channel proteins that underlie the transient and (part of the) sustained currents. Under diabetic and hypothyroid conditions, both currents were also augmented by an endothelin receptor blocker (PD142893) or by an endothelin-converting enzyme inhibitor. Kv4.2 density was also enhanced by PD142893. Incubation (>5 h) with the PKC inhibitor bis-indolylmaleimide augmented both currents, whereas the PKC activator dioctanoyl-rac-glycerol (DiC8) prevented the augmentation of currents by quinapril. DiC8 also prevented the augmentation of Kv4.2 density by quinapril. Specific peptides that activate PKC translocation indicated that PKC-epsilon and not PKC-delta is involved in ANG II action on these currents. In control myocytes, quinapril and PD142893 augmented the sustained late current but had no effect on peak current. It is concluded that an autocrine release of angiotensin and endothelin in diabetic and hypothyroid conditions attenuates K(+) currents by suppressing the synthesis of some K(+) channel proteins, with the effects mediated at least partially by PKC-epsilon. 相似文献
25.
26.
Abraham Fisher Rachel Brandeis Rachel Haring Naomi Eshhar Eliahu Heldman Yishai Karton Orli Eisenberg Haim Meshulam Daniele Marciano Nira Bar-Ner Zipora Pittel 《Journal of Physiology》1998,92(5-6)
M1 selective agonists from the AF series (e.g. AF102B, AF150(S)), via m1 muscarinic receptors, activate distinct signal transductions, enhance amyloid precursors proteins secretion from transfected cells and primary cell cultures, show neurotrophic effects and are beneficial in a variety of animal models for Alzheimer's disease. Such m1 agonists may be effective in the treatment and therapy of Alzheimer's disease.
Résumé
Les agonistes sélectifs de type M1 appartenant à la série AF (par exemple AF102B, AF150(S)) activent de manière sélective certaines routes de transduction du signal via les récepteurs muscariniques de type m1, augmentent la sécrétion de la protéine amyloide par les cellules transfectées et les cultures primaires de cellules, produisent des effets neurotrophiques et se montrent bénéfiques pour une variété de modèles animaux de la maladie d'Alzheimer. De tels agonistes peuvent être efficaces pour traiter et guérir la maladie d'Alzheimer. 相似文献27.
Kim Pham Raz Shimoni Mirren Charnley Mandy J. Ludford-Menting Edwin D. Hawkins Kelly Ramsbottom Jane Oliaro David Izon Stephen B. Ting Joseph Reynolds Grant Lythe Carmen Molina-Paris Heather Melichar Ellen Robey Patrick O. Humbert Min Gu Sarah M. Russell 《The Journal of cell biology》2015,210(6):933-950
During mammalian T cell development, the requirement for expansion of many individual T cell clones, rather than merely expansion of the entire T cell population, suggests a possible role for asymmetric cell division (ACD). We show that ACD of developing T cells controls cell fate through differential inheritance of cell fate determinants Numb and α-Adaptin. ACD occurs specifically during the β-selection stage of T cell development, and subsequent divisions are predominantly symmetric. ACD is controlled by interaction with stromal cells and chemokine receptor signaling and uses a conserved network of polarity regulators. The disruption of polarity by deletion of the polarity regulator, Scribble, or the altered inheritance of fate determinants impacts subsequent fate decisions to influence the numbers of DN4 cells arising after the β-selection checkpoint. These findings indicate that ACD enables the thymic microenvironment to orchestrate fate decisions related to differentiation and self-renewal. 相似文献
28.
Hila Zigdon Alon Savidor Yishai Levin Anna Meshcheriakova Raphael Schiffmann Anthony H. Futerman 《PloS one》2015,10(3)
Gaucher disease, a recessive inherited metabolic disorder caused by defects in the gene encoding glucosylceramidase (GlcCerase), can be divided into three subtypes according to the appearance of symptoms associated with central nervous system involvement. We now identify a protein, glycoprotein non-metastatic B (GPNMB), that acts as an authentic marker of brain pathology in neurological forms of Gaucher disease. Using three independent techniques, including quantitative global proteomic analysis of cerebrospinal fluid (CSF) in samples from Gaucher disease patients that display neurological symptoms, we demonstrate a correlation between the severity of symptoms and GPNMB levels. Moreover, GPNMB levels in the CSF correlate with disease severity in a mouse model of Gaucher disease. GPNMB was also elevated in brain samples from patients with type 2 and 3 Gaucher disease. Our data suggest that GPNMB can be used as a marker to quantify neuropathology in Gaucher disease patients and as a marker of treatment efficacy once suitable treatments towards the neurological symptoms of Gaucher disease become available. 相似文献
29.
Retinoic acid inhibits growth in agarose of early chick embryonic cells and may be involved in regulation of axis formation 总被引:1,自引:0,他引:1
The mechanisms involved in the generation of axial structures in the chick are well documented, yet, little is known about the actual factors that generate such a complex pattern. The recent demonstrations that all-trans-retinoic acid (RA) acts as a morphogen during limb development (Thaller and Eichele, 1987) lead us to examine whether during axis formation in the developing chick, RA could be one of the factors involved. We now show that retinoic acid can block a very unusual property of normal early chick embryonic cells, mainly their capacity to grow in semisolid medium. We also present experiments that suggest that RA may play a direct role during axis formation in the developing chick. 相似文献
30.