全文获取类型
收费全文 | 61篇 |
免费 | 3篇 |
专业分类
耳鼻咽喉 | 3篇 |
妇产科学 | 2篇 |
基础医学 | 7篇 |
口腔科学 | 1篇 |
临床医学 | 2篇 |
内科学 | 10篇 |
神经病学 | 14篇 |
外科学 | 3篇 |
综合类 | 1篇 |
预防医学 | 4篇 |
眼科学 | 4篇 |
药学 | 9篇 |
中国医学 | 2篇 |
肿瘤学 | 2篇 |
出版年
2022年 | 1篇 |
2021年 | 3篇 |
2020年 | 2篇 |
2017年 | 5篇 |
2016年 | 3篇 |
2015年 | 2篇 |
2014年 | 2篇 |
2013年 | 4篇 |
2012年 | 2篇 |
2011年 | 5篇 |
2010年 | 1篇 |
2009年 | 2篇 |
2008年 | 3篇 |
2007年 | 6篇 |
2006年 | 5篇 |
2005年 | 4篇 |
2004年 | 8篇 |
2003年 | 2篇 |
2002年 | 3篇 |
1999年 | 1篇 |
排序方式: 共有64条查询结果,搜索用时 78 毫秒
1.
M Rosario Sepúlveda Matias Hidalgo-Sánchez Daniel Marcos Ana M Mata 《Developmental dynamics》2007,236(5):1227-1236
The plasma membrane Ca(2+)-ATPase (PMCA) is highly expressed in the nervous system, but little information is available about its implication in neuronal development. We have analyzed the expression and localization of different isoforms of PMCA in membrane vesicles and sections of chick cerebellum from embryonic day 10 to hatching. We found that the relative amount of each PMCA isoform and their spatiotemporal distribution in the cerebellum are directly linked to precise cellular types during the cerebellar maturation, even in a non-neural tissue as choroid plexus. Purkinje cells contain the highest diversity of PMCA isoforms of the cerebellar cortex since the moment of its morphogenesis. From embryonic day 15, the PMCA2 was highly expressed in the whole Purkinje cell, while PMCAs 1 and 3 had a more restricted distribution in the soma and dendritic branches, and these distributions were evolving according with cell maturation. Other cellular types seem to contain a specific combination of isoforms, but with a well-defined distribution pattern at late moments of development. Thus, PMCAs 1 and 3 were located in the soma of molecular layer interneurons, and only the PMCA2 was observed in granule cells at hatching. Furthermore, PMCA isoforms are also expressed in cellular compartments characterized by a high amount of synapses, suggesting a key role of these proteins in synaptogenesis and in the maturation of neuronal electrophysiological properties. 相似文献
2.
Atul Maheshwari Michael Fischer Pierluigi Gambetti Alicia Parker Aarthi Ram Claudio Soto Luis Concha-Marambio Yvonne Cohen Ermias D. Belay Ryan A. Maddox Simon Mead Clay Goodman Joseph S. Kass Lawrence B. Schonberger Haitham M. Hussein 《Emerging infectious diseases》2015,21(5):750-759
Variant Creutzfeldt-Jakob disease (vCJD) is a rare, fatal prion disease resulting from transmission to humans of the infectious agent of bovine spongiform encephalopathy. We describe the clinical presentation of a recent case of vCJD in the United States and provide an update on diagnostic testing. The location of this patient’s exposure is less clear than those in the 3 previously reported US cases, but strong evidence indicates that exposure to contaminated beef occurred outside the United States more than a decade before illness onset. This case exemplifies the persistent risk for vCJD acquired in unsuspected geographic locations and highlights the need for continued global surveillance and awareness to prevent further dissemination of vCJD. 相似文献
3.
Mark Korthals Laura Tech Kristina Langnaese Anna Gottfried Johannes Hradsky Ulrich Thomas Ana Claudia Zenclussen Monika C. Brunner-Weinzierl Kerry Tedford Klaus-Dieter Fischer 《European journal of immunology》2021,51(3):594-602
The amplitude and duration of Ca2+ signaling is crucial for B-cell development and self-tolerance; however, the mechanisms for terminating Ca2+ signals in B cells have not been determined. In lymphocytes, plasma membrane Ca2+ ATPase (PMCA) isoforms 1 and 4 (PMCA1 and PMCA4, aka ATP2B1 and ATP2B4) are the main candidates for expelling Ca2+ from the cell through the plasma membrane. We report here that Pmca4 (Atp2b4) KO mice had normal B-cell development, while mice with a conditional KO of Pmca1 (Atp2b1) had greatly reduced numbers of B cells, particularly splenic follicular B cells, marginal zone B cells, and peritoneal B-1a cells. Mouse and naïve human B cells showed only PMCA1 expression and no PMCA4 by western blot, in contrast to T cells, which did express PMCA4. Calcium handling was normal in Pmca4−/− B cells, but Pmca1 KO B cells had elevated basal levels of Ca2+, elevated levels in ER stores, and reduced Ca2+ clearance. These findings show that the PMCA1 isoform alone is required to ensure normal B-cell Ca2+ signaling and development, which may have implications for therapeutic targeting of PMCAs and Ca2+ in B cells. 相似文献
4.
5.
天麻钩藤饮对SHR血管平滑肌细胞CaL-α1C及PMCA1 mRNA表达的影响 总被引:1,自引:0,他引:1
目的:观察天麻钩藤饮对自发性高血压大鼠(SHR)血管平滑肌细胞膜L-型电压依赖性钙通道α1C亚单位(CaLα1C)和质膜Ca2+-ATP酶(PMCA)mRNA表达的影响.方法:选用12周龄自发性高血压6性大鼠45只,随机分为5组:天麻钩藤饮组(A组)、天麻钩藤饮去石决明组(B组)、硝苯地平组(C组)、石决明组(D组)、生理盐水组(E组),分别予以天麻钩藤饮水煎液、天麻钩藤饮去石决明水煎液、硝苯地平水溶液、石决明水煎液、生理盐水灌胃给药,每日1次,连续4周.以RT-PCR半定量法检测血管平滑肌细胞CaL-α1C、PMCA1 mRNA的表达水平.结果:用药4周后,天麻钩藤饮、天麻钩藤饮去石决明、硝苯地平对血管平滑肌细胞CaL-α1C mRNA表达均有显著的抑制作用,对PMCA1 mRNA表达均有显著上调作用,石决明未见显著的调控作用.结论:天麻钩藤饮可有效的抑制CaL-α1C的表达,同时促进PMCA1的表达,改善高血压时平滑肌细胞的钙超载状态. 相似文献
6.
Antonella Muscella Nadia Calabriso Carla Vetrugno Francesco Paolo Fanizzi Sandra Angelica De Pascali Carlo Storelli Santo Marsigliante 《Biochemical pharmacology》2011,(1):91
It was previously demonstrated that [Pt(O,O′-acac)(γ-acac)(DMS)] exerted toxic effects at high doses, whilst sub-cytotoxic concentrations induced anoikis and decreased cell migration. Aim of this study was to investigate the hypothesis that [Pt(O,O′-acac)(γ-acac)(DMS)] alters the [Ca2+]i and that this is linked to its ability to trigger rapid apoptosis in MCF-7 cells. Thus, cells were treated with [Pt(O,O′-acac)(γ-acac)(DMS)] and its effects on some of the systems regulating Ca2+ homeostasis were studied, also in cells dealing with the complex changes occurring during the Ca2+ signalling evoked by extracellular stimuli. [Pt(O,O′-acac)(γ-acac)(DMS)] caused the decrease of PMCA activity (but not SERCA or SPCA) and Ca2+ membrane permeability. These two opposite effects on [Ca2+]i resulted in its overall increase from 102 ± 12 nM to 250 ± 24 nM after 15 min incubation. The effects of [Pt(O,O′-acac)(γ-acac)(DMS)] were also evident when cells were stimulated with ATP: the changes in Ca2+ levels caused by purinergic stimulation resulted altered due to decreased PMCA activity and to the closure of Ca2+ channels opened by purinergic receptor. Conversely, [Pt(O,O′-acac)(γ-acac)(DMS)] did not affect the store-operated Ca2+ channels opened by thapsigargin or by ATP. [Pt(O,O′-acac)(γ-acac)(DMS)] provoked the activation of PKC-α and the production of ROS that were responsible for the Ca2+ permeability and PMCA activity decrease, respectively. The overall effect of [Pt(O,O′-acac)(γ-acac)(DMS)] is to increase the [Ca2+]i, an effect that is likely to be linked to its ability to trigger rapid apoptosis in MCF-7 cells. These data reinforce the notion that [Pt(O,O′-acac)(γ-acac)(DMS)] would be a promising drug in cancer treatment. 相似文献
7.
Redox regulation is important for the modulation of cytosolic Ca(2+) concentration. Hence, we have investigated the effect of H(2)O(2) on store-mediated Ca(2+) entry (SMCE). In fura-2-loaded human platelets treatment with H(2)O(2) resulted in a concentration-dependent increase in Ca(2+) release from intracellular stores, while the effect on Ca(2+) entry was biphasic. In addition, 1mM H(2)O(2) reduced SMCE induced by agonists. The inhibitory effect of 1mM H(2)O(2) was prevented by inhibition of actin polymerization with cytochalasin D. Consistent with this, we found that 10microM H(2)O(2) and store depletion by treatment with thapsigargin plus ionomycin induced a similar temporal sequence of actin reorganization, while exposure to 1mM H(2)O(2) shifted the dynamics between polymerization and depolymerization in favor of the former. One millimolar H(2)O(2)-induced polymerization was reduced by treatment with methyl 2,5-dihydroxycinnamate and farnesylthioacetic acid, inhibitors of tyrosine kinases and Ras superfamily proteins, respectively. Finally, exposure to 1mM H(2)O(2) significantly increased store depletion-induced p60(src) activation. We conclude that H(2)O(2) exerted a biphasic effect on SMCE. The inhibitory role of high H(2)O(2) concentrations is mediated by an abnormal actin reorganization pattern involving both Ras- and tyrosine kinases-dependent pathways. 相似文献
8.
Calcium extrusion protein expression in the hippocampal formation of chronic epileptic rats after kainate-induced status epilepticus 总被引:3,自引:0,他引:3
PURPOSE: The plasma membrane Ca2+ -adenosine triphosphatase (ATPase) (PMCA) and (potassium-dependent) sodium-calcium exchange [NC(K)X] represent two main calcium-extrusion mechanisms that are important for the restoration of [Ca2+]i levels after electrical activity. We investigated whether the expression of these calcium-extrusion proteins is altered in the course of epileptogenesis. METHODS: Hippocampal-parahippocampal protein expression of NCX1, 2, and 3, PMCA1-4, and NCKX2 at an early and late stage after kainate-induced status epilepticus (SE) was compared with that in control rats by using immunocytochemistry. RESULTS: Several alterations were found in chronic epileptic rats: (a) NCX1 expression was permanently decreased in the inner molecular layer (IML) of the dentate gyrus (DG) and entorhinal cortex layer III (ECIII), related to neuronal loss in hilus and ECIII, respectively; (b) PMCA and NCKX2 expression was transiently upregulated in the IML, and decreased in several areas where cell loss had occurred, (c) NCX3 expression, which in control rats is abundant in presynaptic terminals of mossy fibers (MF), was extensively and permanently decreased in stratum lucidum and hilar region. In addition, newly formed MF sprouts that project to the DG iml did not noticeably express NCX3; (d) NCX2 and NCKX2 were (transiently) upregulated in astrocytes of epileptic rats throughout the hippocampal formation, including ECIII. CONCLUSIONS: These region-specific changes in calcium-extrusion proteins reflect a change in calcium regulation. Whether these regional-specific changes of calcium-extrusion proteins are associated with an abnormal calcium homeostasis must be determined. Because some alterations of calcium-extrusion protein expression are already present at an early stage of epileptogenesis, they could be involved in this process. 相似文献
9.
BACKGROUND: Rat coagulating gland epithelial cells export proteins by an apocrine secretion mode within membrane blebs arising from the apical plasma membrane. Using a pan-PMCA antibody, we have recently shown the plasma membrane Ca(2+)-ATPase (PMCA) being part of the apical plasma membrane of epithelial cells and incorporated into the aposomal membrane. The mRNA of PMCA isoforms 1 and 4 respectively, have been detected by RT-PCR in rat coagulating gland. METHODS: In order to identify which PMCA isoform is integrated into aposomes during apocrine secretion and whether or not PMCA export is influenced by androgens RT-PCR, in situ hybridization, Western blotting, and immunofluorescence experiments were performed. RESULTS: PMCA1b is the isoform which is expressed and located in the apical plasma membrane of coagulating gland epithelial cells and is integrated into the aposomal membrane. In contrast, PMCA4 mRNA and protein are restricted to the stroma. Androgen deprivation by castration within 14 days leads to an accumulation of PMCA1b in coagulating gland epithelium, while aposomes are not detected anymore. CONCLUSIONS: We showed for the first time that PMCA isoform 1b is released via aposomes of the epithelial cells of the rat coagulating gland and that the localization of PMCA1b in the epithelial cells is influenced by androgens. 相似文献
10.