全文获取类型
收费全文 | 154篇 |
免费 | 23篇 |
国内免费 | 4篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 2篇 |
2018年 | 4篇 |
2017年 | 2篇 |
2016年 | 8篇 |
2015年 | 11篇 |
2014年 | 14篇 |
2013年 | 5篇 |
2012年 | 11篇 |
2011年 | 9篇 |
2010年 | 6篇 |
2009年 | 8篇 |
2008年 | 9篇 |
2007年 | 5篇 |
2006年 | 4篇 |
2005年 | 6篇 |
2004年 | 8篇 |
2003年 | 5篇 |
2002年 | 5篇 |
2001年 | 5篇 |
2000年 | 5篇 |
1999年 | 3篇 |
1998年 | 8篇 |
1997年 | 4篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 4篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1985年 | 1篇 |
1983年 | 4篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1978年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有181条查询结果,搜索用时 15 毫秒
111.
Vaughn M van Oorschot R Baindur-Hudson S 《American journal of physical anthropology》2008,137(1):91-96
Pigmentation of hair in humans has been investigated by medical scientists, anthropologists and, more recently, by forensic scientists. In every investigation, hair color must first be defined by the researchers. Subjective color assessment inhibits the reproducibility of experiments and the direct comparison of results. The aim of this study was to objectively measure human hair color and examine the variation found in a population with European ancestry, using the CIE L*a*b* color space. Observer-perceived hair colors were compared with self-reported hair colors and the color as measured by reflective spectrophotometry of 132 subjects of European ancestry. The presented data show that self-reported hair colors and observer-reported colors are similar; however, these categories are not necessarily the best way to categorize hair color for quantitative research. Using a two-step cluster analysis, hair color can be divided into categories or clusters based on spectrophotometric measurements in the CIE L*a*b* color space and these clusters can be well discriminated from each other. This separation is primarily based on the b* (yellow) color component and the clusters show agreement to observer-reported colors. This study illustrates the possibilities for and necessity of objectively defining the hair color phenotype for various downstream applications. 相似文献
112.
Dubé N Kooistra MR Pannekoek WJ Vliem MJ Oorschot V Klumperman J Rehmann H Bos JL 《Cellular signalling》2008,20(9):1608-1615
The small G-protein Rap1 is a critical regulator of cell-cell contacts and is activated by the remodeling of adherens junctions. Here we identify the Rap1 guanine nucleotide exchange factor PDZ-GEF2 as an upstream activator of Rap1 required for the maturation of adherens junctions in the lung carcinoma cells A549. Knockdown of PDZ-GEF2 results in the persistence of adhesion zippers at cell-cell contacts. Activation of Rap1A rescues junction maturation in absence of PDZ-GEF2, demonstrating that Rap1A is downstream of PDZ-GEF2 in this process. Moreover, depletion of Rap1A, but not Rap1B, impairs adherens junction maturation. siRNA for PDZ-GEF2 also lowers the levels of E-cadherin, an effect that can be mimicked by Rap1B, but not Rap1A siRNA. Since junctions in Rap1B depleted cells have a mature appearance, these data suggest that PDZ-GEF2 activates Rap1A and Rap1B to perform different functions. Our results present the first direct evidence that PDZ-GEF2 plays a critical role in the maturation of adherens junctions. 相似文献
113.
Zirconyl hematoxylin stains acidic mucins darkly and specifically using a solution of 100 mg hematoxylin, 5 ml ethanol, 5 ml 0.5% sodium iodate, 400 mg zirconyl chloride octahydrate, and 30 ml 25% aqueous glycerol. The stain is especially advantageous for studying goblet cells and Paget cells. 相似文献
114.
Jared R. Helm Marvin Bentley Kevin D. Thorsen Ting Wang Lauren Foltz Viola Oorschot Judith Klumperman Jesse C. Hay 《The Journal of biological chemistry》2014,289(34):23609-23628
Luminal calcium released from secretory organelles has been suggested to play a regulatory role in vesicle transport at several steps in the secretory pathway; however, its functional roles and effector pathways have not been elucidated. Here we demonstrate for the first time that specific luminal calcium depletion leads to a significant decrease in endoplasmic reticulum (ER)-to-Golgi transport rates in intact cells. Ultrastructural analysis revealed that luminal calcium depletion is accompanied by increased accumulation of intermediate compartment proteins in COPII buds and clusters of unfused COPII vesicles at ER exit sites. Furthermore, we present several lines of evidence suggesting that luminal calcium affected transport at least in part through calcium-dependent interactions between apoptosis-linked gene-2 (ALG-2) and the Sec31A proline-rich region: 1) targeted disruption of ALG-2/Sec31A interactions caused severe defects in ER-to-Golgi transport in intact cells; 2) effects of luminal calcium and ALG-2/Sec31A interactions on transport mutually required each other; and 3) Sec31A function in transport required luminal calcium. Morphological phenotypes of disrupted ALG-2/Sec31A interactions were characterized. We found that ALG-2/Sec31A interactions were not required for the localization of Sec31A to ER exit sites per se but appeared to acutely regulate the stability and trafficking of the cargo receptor p24 and the distribution of the vesicle tether protein p115. These results represent the first outline of a mechanism that connects luminal calcium to specific protein interactions regulating vesicle trafficking machinery. 相似文献
115.
Oueslati M Hermosilla R Schönenberger E Oorschot V Beyermann M Wiesner B Schmidt A Klumperman J Rosenthal W Schülein R 《The Journal of biological chemistry》2007,282(28):20676-20685
Mutant membrane proteins are frequently retained in the early secretory pathway by a quality control system, thereby causing disease. An example are mutants of the vasopressin V(2) receptor (V(2)R) leading to nephrogenic diabetes insipidus. Transport-defective V(2)Rs fall into two classes: those retained exclusively in the endoplasmic reticulum (ER) and those reaching post-ER compartments such as the ER/Golgi intermediate compartment. Although numerous chemical or pharmacological chaperones that rescue the transport of ER-retained membrane proteins are known, substances acting specifically in post-ER compartments have not been described as yet. Using the L62P (ER-retained) and Y205C (reaching post-ER compartments) mutants of the V(2)R as a model, we show here that the cell-penetrating peptide penetratin and its synthetic analog KLAL rescue the transport of the Y205C mutant. In contrast, the location of the L62P mutant is not influenced by either peptide because the peptides are unable to enter the ER. We also show data indicating that the peptide-mediated transport rescue is associated with an increase in cytosolic Ca(2+) concentrations. Thus, we describe a new class of substances influencing protein transport specifically in post-ER compartments. 相似文献
116.
Thymol and Carvacrol Prevent Cisplatin‐Induced Nephrotoxicity by Abrogation of Oxidative Stress,Inflammation, and Apoptosis in Rats 下载免费PDF全文
El‐Sayed EM Abd‐Allah AR Mansour AM EL‐Arabey AA 《Journal of biochemical and molecular toxicology》2015,29(4):165-172
The aim of the present study is to assess the possible protective effects of thymol and carvacrol against cisplatin (CP)‐induced nephrotoxicity. A single dose of CP {6 mg/kg, intraperitoneally (i.p.)} injected to male rats revealed significant increases in serum urea, creatinine, and tumor necrosis factor alpha levels. It also increased kidney contents of malondialdehyde and caspase‐3 activity with significant reduction in serum albumin, kidney content of reduced glutathione as well as catalase, and superoxide dismutase activity as compared to that of the control group. In contrast, administration of thymol {20 mg/kg, orally (p.o.)} and/or carvacrol (15 mg/kg, p.o.) for 14 days before CP injection and for 7 days after CP administration restored the kidney function and examined oxidative stress parameters. In conclusion, thymol was more effective nephroprotective than carvacrol. Moreover, a combination of thymol and carvacrol had a synergistic nephroprotective effect that might be attributed to antioxidant, anti‐inflammatory, and antiapoptotic activities. 相似文献
117.
Bax NA Pijnappels DA van Oorschot AA Winter EM de Vries AA van Tuyn J Braun J Maas S Schalij MJ Atsma DE Goumans MJ Gittenberger-de Groot AC 《Journal of cellular and molecular medicine》2011,15(12):2675-2683
The myocardium of the developing heart tube is covered by epicardium. These epicardial cells undergo a process of epithelial-to-mesenchymal transformation (EMT) and develop into epicardium-derived cells (EPDCs). The ingrowing EPDCs differentiate into several celltypes of which the cardiac fibroblasts form the main group. Disturbance of EMT of the epicardium leads to serious hypoplasia of the myocardium, abnormal coronary artery differentiation and Purkinje fibre paucity. Interestingly, the electrophysiological properties of epicardial cells and whether EMT influences electrical conductivity of epicardial cells is not yet known. We studied the electrophysiological aspects of epicardial cells before and after EMT in a dedicated in vitro model, using micro-electrode arrays to investigate electrical conduction across epicardial cells. Therefore, human adult epicardial cells were placed between two neonatal rat cardiomyocyte populations. Before EMT the epicardial cells have a cobblestone (epithelium-like) phenotype that was confirmed by staining for the cell-adhesion molecule β-catenin. After spontaneous EMT in vitro the EPDCs acquired a spindle-shaped morphology confirmed by vimentin staining. When comparing both types we observed that the electrical conduction is influenced by EMT, resulting in significantly reduced conductivity of spindle-shaped EPDCs, associated with a conduction block. Furthermore, the expression of both gap junction (connexins 40, Cx43 and Cx45) and ion channel proteins (SCN5a, CACNA1C and Kir2.1) was down-regulated after EMT. This study shows for the first time the conduction differences between epicardial cells before and after EMT. These differences may be of relevance for the role of EPDCs in cardiac development, and in EMT-related cardiac dysfunction. 相似文献
118.
Schmitz JP Jeneson JA van Oorschot JW Prompers JJ Nicolay K Hilbers PA van Riel NA 《PloS one》2012,7(3):e34118
The regulation of the 100-fold dynamic range of mitochondrial ATP synthesis flux in skeletal muscle was investigated. Hypotheses of key control mechanisms were included in a biophysical model of oxidative phosphorylation and tested against metabolite dynamics recorded by 31P nuclear magnetic resonance spectroscopy (31P MRS). Simulations of the initial model featuring only ADP and Pi feedback control of flux failed in reproducing the experimentally sampled relation between myoplasmic free energy of ATP hydrolysis (ΔGp = ΔGp
o′+RT ln ([ADP][Pi]/[ATP]) and the rate of mitochondrial ATP synthesis at low fluxes (<0.2 mM/s). Model analyses including Monte Carlo simulation approaches and metabolic control analysis (MCA) showed that this problem could not be amended by model re-parameterization, but instead required reformulation of ADP and Pi feedback control or introduction of additional control mechanisms (feed forward activation), specifically at respiratory Complex III. Both hypotheses were implemented and tested against time course data of phosphocreatine (PCr), Pi and ATP dynamics during post-exercise recovery and validation data obtained by 31P MRS of sedentary subjects and track athletes. The results rejected the hypothesis of regulation by feed forward activation. Instead, it was concluded that feedback control of respiratory chain complexes by inorganic phosphate is essential to explain the regulation of mitochondrial ATP synthesis flux in skeletal muscle throughout its full dynamic range. 相似文献
119.
Background
Breast cancer survivors, particularly those treated with chemotherapy, are at significantly increased risk for long-term cognitive and neurobiologic impairments. These deficits tend to involve skills that are subserved by distributed brain networks. Additionally, neuroimaging studies have shown a diffuse pattern of brain structure changes in chemotherapy-treated breast cancer survivors that might impact large-scale brain networks.Methods
We therefore applied graph theoretical analysis to compare the gray matter structural networks of female breast cancer survivors with a history of chemotherapy treatment and healthy age and education matched female controls.Results
Results revealed reduced clustering coefficient and small-world index in the brain network of the breast cancer patients across a range of network densities. In addition, the network of the breast cancer group had less highly interactive nodes and reduced degree/centrality in the frontotemporal regions compared to controls, which may help explain the common impairments of memory and executive functioning among these patients.Conclusions
These results suggest that breast cancer and chemotherapy may decrease regional connectivity as well as global network organization and integration, reducing efficiency of the network. To our knowledge, this is the first report of altered large-scale brain networks associated with breast cancer and chemotherapy. 相似文献120.
PJ Walser N Ariotti M Howes C Ferguson R Webb D Schwudke N Leneva KJ Cho L Cooper J Rae M Floetenmeyer VM Oorschot U Skoglund K Simons JF Hancock RG Parton 《Cell》2012,150(4):752-763
Caveolin plays an essential role in the formation of characteristic surface pits, caveolae, which cover the surface of many animal cells. The fundamental principles of caveola formation are only slowly emerging. Here we show that caveolin expression in a prokaryotic host lacking any intracellular membrane system drives the formation of cytoplasmic vesicles containing polymeric caveolin. Vesicle formation is induced by expression of wild-type caveolins, but not caveolin mutants defective in caveola formation in mammalian systems. In addition, cryoelectron tomography shows that the induced membrane domains are equivalent in size and caveolin density to native caveolae and reveals a possible polyhedral arrangement of caveolin oligomers. The caveolin-induced vesicles or heterologous caveolae (h-caveolae) form by budding in from the cytoplasmic membrane, generating a membrane domain with distinct lipid composition. Periplasmic solutes are encapsulated in the budding h-caveola, and purified h-caveolae can be tailored to be targeted to specific cells of interest. 相似文献