全文获取类型
收费全文 | 195篇 |
免费 | 42篇 |
国内免费 | 1篇 |
出版年
2024年 | 1篇 |
2023年 | 3篇 |
2022年 | 3篇 |
2021年 | 10篇 |
2020年 | 6篇 |
2019年 | 6篇 |
2018年 | 9篇 |
2017年 | 14篇 |
2016年 | 8篇 |
2015年 | 11篇 |
2014年 | 13篇 |
2013年 | 15篇 |
2012年 | 6篇 |
2011年 | 10篇 |
2010年 | 6篇 |
2009年 | 5篇 |
2008年 | 9篇 |
2007年 | 11篇 |
2006年 | 13篇 |
2005年 | 9篇 |
2004年 | 9篇 |
2003年 | 6篇 |
2002年 | 5篇 |
2001年 | 2篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 2篇 |
1997年 | 5篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1993年 | 4篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1986年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 3篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1973年 | 3篇 |
排序方式: 共有238条查询结果,搜索用时 203 毫秒
231.
The adipokine leptin and oncotic protein albumin are endocytosed in the proximal tubule via the scavenger receptor megalin. Leptin reduces megalin expression and activates cell signalling pathways that upregulate fibrotic protein expression. The aim of this study was to investigate if leptin uptake in proximal tubule cells was via the albumin-megalin endocytic complex. In immortalised proximal tubule Opossum kidney cells (OK) fluorescent leptin and albumin co-localised following 5 min exposure, however there was no co-localisation at 10, 20 and 30 min exposure. In OK cells, acute exposure to leptin for 2 h did not alter NHE3, ClC-5, NHERF1 and NHERF2 mRNA. However, acute leptin exposure increased NHERF2 protein expression in proximal tubule cells. In OK cells, immunoprecipitation experimentation indicated leptin did not bind to ClC-5. Leptin uptake in OK cells was enhanced by bafilomycin and ammonium chloride treatment, demonstrating that uptake was not dependent on lysosomal pH. Thus, it is likely that two pools of megalin exist in proximal tubule cells to facilitate separate uptake of leptin and albumin by endocytosis. 相似文献
232.
233.
Craig C. Beeson 《Analytical biochemistry》2010,404(1):75-81
Mitochondria are a common target of toxicity for drugs and other chemicals and result in decreased aerobic metabolism and cell death. In contrast, mitochondrial biogenesis restores cell vitality, and there is a need for new agents to induce biogenesis. Current cell-based models of mitochondrial biogenesis or toxicity are inadequate because cultured cell lines are highly glycolytic with minimal aerobic metabolism and altered mitochondrial physiology. In addition, there are no high-throughput real-time assays that assess mitochondrial function. We adapted primary cultures of renal proximal tubular cells (RPTCs) that exhibit in vivo levels of aerobic metabolism, are not glycolytic, and retain higher levels of differentiated functions and used the Seahorse Bioscience analyzer to measure mitochondrial function in real time in multiwell plates. Using uncoupled respiration as a marker of electron transport chain (ETC) integrity, the nephrotoxicants cisplatin, HgCl2, and gentamicin exhibited mitochondrial toxicity prior to decreases in basal respiration and cell death. Conversely, using FCCP (carbonylcyanide p-trifluoromethoxyphenylhydrazone)-uncoupled respiration as a marker of maximal ETC activity, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), SRT1720, resveratrol, daidzein, and metformin produced mitochondrial biogenesis in RPTCs. The merger of the RPTC model and multiwell respirometry results in a single high-throughput assay to measure mitochondrial biogenesis and toxicity and nephrotoxic potential. 相似文献
234.
V. Marshansky A. Fleser J. Noël S. Bourgoin P. Vinay 《The Journal of membrane biology》1996,153(1):59-73
During the preparation of a suspension of dog kidney proximal tubules by collagenase treatment, an uptake of FITC-albumin
was demonstrated. This process is attributed to the activation of receptor-mediated endocytosis leading to the appearance
of FITC-albumin into intracellular vesicular structures. The isolation of brush border membrane vesicles (BBMV) from the dog
kidney proximal tubules in suspension by the magnesium precipitation technique leads to the copurification of a large population
of endosomes. These endosomes were separated from BBM vesicles by a technique involving wheat-germ agglutinin. The enrichment
in BBM markers and in bafilomycin-sensitive ATPase activity was comparable in endosomes and BBM vesicles. However, the acridine
orange acidification assay showed a V-type ATPase-dependent acidification in endosomes but not in BBMV, demonstrating a different
orientation of the proton pumps in these structures. SDS-PAGE analysis also showed significant differences in protein pattern
of vesicles and endosomes. The most notable difference was the presence of 42–44 kDa and 20–24 kDa proteins in BBMV and their
complete absence in endosomes. Western blot analysis identified these proteins as actin and RhoA, among other small proteins,
respectively. Western blot experiments also demonstrated a different distribution of β-COP, β-adaptin, and RhoGDI in vesicles
and endosomes. The morphological aspect (electron microscopy) and sedimentation of endosomes in a 50% Percoll gradient identified
these structures as ``heavy endosomes' (buoyant density D= 1.036 g/ml). Flow cytometry analysis of heavy endosomes purified from tubules isolated in presence of FITC-albumin showed
the presence of FITC-albumin in up to 92% of these intracellular organelles. Western blot analysis using anti-FITC and anti-collagenase
antibodies allowed quantification of the FITC-albumin and collagenase A in the purified endosomes. Our results indicate that
heavy endosomes are formed during the preparation of the proximal tubules following activation of receptor-mediated endocytosis,
probably by soluble proteins. The suspension of tubules thus offers a experimental tool to study the protein reabsorption
and traffic of endosomal vesicles in the proximal tubules.
Received: 13 July 1995/Revised: 8 May 1996 相似文献
235.
Román Jiménez-Vera Oscar Monroy Alma Corona-Cruz Mariano García-Garibay 《World journal of microbiology & biotechnology》2008,24(12):2767-2774
The objective of the present study was to construct a system that re-creates the conditions of fermentation and absorption
of the human proximal colon. The model was constructed using a glass tube with an internal dialysis membrane tube. The food
substrate was fed into the dialysis membrane three times a day simulating a typical human feeding. The substrate contained
58% carbohydrates, 35% proteins, 3% fiber, 3% starch, and 1% lipids on dry weight base, with 90% moisture. The inoculum was
a fecal culture propagated in TSB. The intestinal absorption was simulated using a polyethylene glycol (PEG) solution running
continuously outside the dialysis membrane. All microorganisms increased their counts after inoculation, and reached higher
counts generally after substrate feed. The most important short chain fatty acids (SCFA: acetic, propionic and butyric acids)
were analyzed, and their concentrations inside and outside the membrane were significantly different due to the extraction
efficiency of the PEG solution. The greatest production occurred at 48 h. SCFA ratios showed that at the beginning, acetate
was the predominant compound, but after 12 h the proportion of butyrate increased and the acetate was decreased. This SCFA
production pattern is similar to that reported for the proximal colon in live systems. Continuous operation of the colon model
for 48 h was enough to reveal the development of microorganisms and SCFA production. This model reproduced the conditions
of the human proximal colon adequately and can be used to study the development of colonic microbiota. 相似文献
236.
Coral García-Pastor Rafael Blázquez-Serra Ricardo J. Bosch Francisco J. Lucio Cazaña Ana B. Fernández-Martínez 《生物化学与生物物理学报:疾病的分子基础》2019,1865(9):2504-2515
The therapeutic efficacy of the antineoplastic drug cisplatin is limited by its nephrotoxicity, which affects particularly to proximal tubular cells (PTC). Cisplatin-induced cytotoxicity appears to be multifactorial and involves inflammation, oxidative stress as well as apoptosis. We have recently shown that the cyclo-oxygenase-2 (COX-2)/intracellular prostaglandin E2 (iPGE2)/EP receptor pathway mediates the apoptotic effect of cisplatin on human proximal tubular HK-2 cells. Here, we studied the effects on HK-2 cells of apoptotic bodies (ABs) generated after treatment of HK-2 cells with cisplatin. We found that ABs inhibited cell growth, induced apoptosis and increased COX-2 expression and iPGE2 in ABs-recipient HK-2 cells. Inhibition of the COX-2/iPGE2/EP receptor pathway in these cells prevented the effects of ABs without interfering with their internalization. Interestingly, 2nd generation ABs (i.e. ABs released by cells undergoing apoptosis upon treatment with ABs) did not trigger apoptosis in naïve HK-2 cells, and stimulated cell proliferation through the COX-2/iPGE2/EP receptor pathway. These results suggest that ABs, through iPGE2-dependent mechanisms, might have a relevant role in the natural history of cisplatin-induced acute kidney failure because they contribute first to the propagation of the noxious effects of cisplatin to non-injured PTC and then to the promotion of the proliferative tubular response required for proximal tubule repair. Since iPGE2 also mediates both cisplatin-induced HK-2 cell apoptosis, intervention in the COX-2/iPGE2/EP receptor pathway might provide us with new therapeutic avenues in patients with cisplatin-induced acute kidney injury. 相似文献
237.
L. J. Schep I. G. Tucker G. Young A. G. Butt 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1997,167(5):370-377
The objective of this study was to assess regional variations in the permeability of the salmon posterior intestine and to
evaluate the effect of permeability enhancers as a basis for oral delivery of biologically active peptides. Proximal and distal
portions of the posterior intestine of the chinook salmon (Oncorhynchus tshawytscha) were removed, mounted as flat sheets in Ussing chambers and superfused with trout Ringer's. Intestinal permeability was
assessed under short-circuit conditions by measurement of 14C-mannitol (mucosal to serosal) flux. Tissues were treated either with the mucolytic agent dithiothreitol (10 mmol · l−1), the permeability enhancer sodium deoxycholate (5.0 mmol · l−1) or both and compared to untreated controls. Both proximal and distal control tissues had low permeabilities, but the distal
region had a lower transepithelial electrical resistance and produced significantly less mucus. Treatment with either dithiothreitol
or sodium deoxycholate alone reduced mucus adhering to tissue in both regions but did not increase permeability or change
transepithelial electrical resistance. In the distal region, sequential treatment with both agents significantly reduced adhering
mucus, decreased transepithelial electrical resistance, and increased tissue permeability. The salmon posterior intestine
can be divided into proximal and distal regions. The distal region is more likely to have the necessary permeability and responsiveness
to enhancement for the successful delivery of peptides or polar drugs.
Accepted: 14 January 1997 相似文献
238.
Pi depletion of proximal tubule cells isolated from mouse kidney results in a decrease in the cell content of fructose-2,6-bisphosphate and an increase in the rate of gluconeogenesis from pyruvate, malate and succinate. Gluconeogenesis from glycerol is unaffected by Pi depletion. Introduction of fructose-2,6-bisphosphate into the cytosol of ATP-permeabilized cells is accompanied by a fall in gluconeogenesis. The presence of external Ca2+ stimulates gluconeogenesis. When cytosolic Ca2+ is raised to 1.8 microM by permeabilization, the resealed cells still require 2.5 mM Ca2+ in the bathing medium in order to perform gluconeogenesis at the maximum rate. Cells permeabilized in the presence of cAMP show a decreased rate of glucose production. Phorbol ester stimulates gluconeogenesis provided that the phorbol treatment is performed in the absence of Ca2+ ions. It is suggested that Pi depletion may stimulate pyruvate carboxylase activity and facilitate the entry of certain gluconeogenic substrates into mitochondria. It is also proposed that important aspects of the control of renal gluconeogenesis by parathyroid hormone are mediated by protein kinase C. 相似文献