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81.
Patients with cancer often develop major electrolyte disorders, which are aggravated by radiation therapy and chemotherapy and by the concomitant impairment of the renal function and the development of drug resistance. In addition, tumour cells have membranes with more negative charges than normal eukaryotic cells. This study was designed to test the hypothesis that the ability of the Ca(2+) blocker verapamil to mediate the reversal of multidrug resistance (MDR) by interacting with the membrane phospholipids may be correlated with the ionic strength and membrane surface potential in resistant tumours. The permeation properties of verapamil, which is the best-known MDR-modulator, were therefore studied by quantifying its ability to induce the leakage of carboxyfluorescein through unilamellar liposomes containing various mole fractions of phosphatidic acid (x(EPA)=0, 0.1 and 0.3), at four different ionic strengths (I=0.052, 0.124, 0.204 and 0.318 M). The dye leakage induced by verapamil varied greatly with I, depending on x(EPA). The permeation process was a co-operative one (1.3相似文献
82.
C. Tollenaere S. Jacquet S. Ivanova A. Loiseau J.‐M. Duplantier R. Streiff C. Brouat 《Molecular ecology》2013,22(2):354-367
Genome scans using amplified fragment length polymorphism (AFLP) markers became popular in nonmodel species within the last 10 years, but few studies have tried to characterize the anonymous outliers identified. This study follows on from an AFLP genome scan in the black rat (Rattus rattus), the reservoir of plague (Yersinia pestis infection) in Madagascar. We successfully sequenced 17 of the 22 markers previously shown to be potentially affected by plague‐mediated selection and associated with a plague resistance phenotype. Searching these sequences in the genome of the closely related species Rattus norvegicus assigned them to 14 genomic regions, revealing a random distribution of outliers in the genome (no clustering). We compared these results with those of an in silico AFLP study of the R. norvegicus genome, which showed that outlier sequences could not have been inferred by this method in R. rattus (only four of the 15 sequences were predicted). However, in silico analysis allowed the prediction of AFLP markers distribution and the estimation of homoplasy rates, confirming its potential utility for designing AFLP studies in nonmodel species. The 14 genomic regions surrounding AFLP outliers (less than 300 kb from the marker) contained 75 genes encoding proteins of known function, including nine involved in immune function and pathogen defence. We identified the two interleukin 1 genes (Il1a and Il1b) that share homology with an antigen of Y. pestis, as the best candidates for genes subject to plague‐mediated natural selection. At least six other genes known to be involved in proinflammatory pathways may also be affected by plague‐mediated selection. 相似文献
83.
Claude Moulis Komar R. Wirasutisna Jacqueline Gleye Philippe Loiseau Edouard Stanislas Christian Moretti 《Phytochemistry》1983,22(9):2095-2096
From Almeidea guyanensis, besides N-methylatanine, N-methylflindersine, N-methylkhaplofoline and 4-demethyl-N-methylatanine, a new 2-quinolone, almeine, has been isolated and its structure elucidated as 4-isopropenyl-N-methyl-3,4-dihydrofuro-2-quinolone. 相似文献
84.
J. Nafziger J. J. Guillosson Y. Adam C. Hecquet M. Payard M. Loiseau 《Cytotechnology》1991,6(3):227-232
New derivatives of imidazothiazole and imidazobenzothiazole were testedin vitro for their potential antiproliferative activity. Four imidazobenzothiazole derivatives exhibited a cytotoxic activity against two leukemic cell lines, compound I being the most effective. Cell cycle kinetics studies showed that this drug delays the progression of cells from G1 to S and G2 M phases. An inhibitory effect on DNA and RNA synthesis was also observed. The antiproliferative effect of this compound, analogue of immunosuppressive agents, suggested that it could be of interest for a therapeutic use and for the synthesis of new derivatives. 相似文献
85.
Chevrollier A Loiseau D Chabi B Renier G Douay O Malthièry Y Stepien G 《Journal of bioenergetics and biomembranes》2005,37(5):307-317
The three adenine nucleotide translocator ({ANT1} to {ANT3}) isoforms, differentially expressed in human cells, play a crucial
role in cell bioenergetics by catalyzing ADP and ATP exchange across the mitochondrial inner membrane. In contrast to differentiated
tissue cells, transformed cells, and their ρ0 derivatives, i.e. cells deprived of mitochondrial DNA, sustain a high rate of glycolysis. We compared the expression pattern
of {ANT} isoforms in several transformed human cell lines at different stages of the cell cycle. The level of {ANT2} expression
and glycolytic ATP production in these cell lines were in keeping with their metabolic background and their state of differentiation.
The sensitivity of the mitochondrial inner membrane potential (Δψ) to several inhibitors of glycolysis and oxidative phosphorylation
confirmed this relationship. We propose a new model for ATP uptake in cancer cells implicating the {ANT2} isoform, in conjunction
with hexokinase II and the β subunit of mitochondrial ATP synthase, in the Δψ maintenance and in the aggressiveness of cancer
cells. 相似文献
86.
Désiré L Bourdin J Loiseau N Peillon H Picard V De Oliveira C Bachelot F Leblond B Taverne T Beausoleil E Lacombe S Drouin D Schweighoffer F 《The Journal of biological chemistry》2005,280(45):37516-37525
beta-Amyloid peptides (Abeta) that form the senile plaques of Alzheimer disease consist mainly of 40- and 42-amino acid (Abeta 40 and Abeta 42) peptides generated from the cleavage of the amyloid precursor protein (APP). Generation of Abeta involves beta-secretase and gamma-secretase activities and is regulated by membrane trafficking of the proteins involved in Abeta production. Here we describe a new small molecule, EHT 1864, which blocks the Rac1 signaling pathways. In vitro, EHT 1864 blocks Abeta 40 and Abeta 42 production but does not impact sAPPalpha levels and does not inhibit beta-secretase. Rather, EHT 1864 modulates APP processing at the level of gamma-secretase to prevent Abeta 40 and Abeta 42 generation. This effect does not result from a direct inhibition of the gamma-secretase activity and is specific for APP cleavage, since EHT 1864 does not affect Notch cleavage. In vivo, EHT 1864 significantly reduces Abeta 40 and Abeta 42 levels in guinea pig brains at a threshold that is compatible with delaying plaque accumulation and/or clearing the existing plaque in brain. EHT 1864 is the first derivative of a new chemical series that consists of candidates for inhibiting Abeta formation in the brain of AD patients. Our findings represent the first pharmacological validation of Rac1 signaling as a target for developing novel therapies for Alzheimer disease. 相似文献
87.
Mutations within the MGC4607 gene cause cerebral cavernous malformations 总被引:10,自引:0,他引:10
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Denier C Goutagny S Labauge P Krivosic V Arnoult M Cousin A Benabid AL Comoy J Frerebeau P Gilbert B Houtteville JP Jan M Lapierre F Loiseau H Menei P Mercier P Moreau JJ Nivelon-Chevallier A Parker F Redondo AM Scarabin JM Tremoulet M Zerah M Maciazek J Tournier-Lasserve E;Société Française de Neurochirurgie 《American journal of human genetics》2004,74(2):326-337
88.
C. Clerici S. Couette A. Loiseau P. Herman C. Amiel 《The Journal of membrane biology》1995,147(3):295-304
We have investigated the presence of Na-K-Cl cotransport in alveolar type II cells using uptake of 86Rb. Several data support the presence of a Na-K-Cl cotransport in these cells. First, a large fraction of ouabain-resistant 86Rb uptake was inhibited by bumetanide and furosemide. Second, bumetanide-sensitive 86Rb up-take required the presence of Na+ and Cl– in the incubation medium; dependency on extracellular Na+ and K+ was hyperbolic, with a Km of 14.6 m and 8.3 m, respectively, while dependency on extracellular Cl– was sigmoidal, which suggests a 112 stoichiometry. Third, a fraction of amiloride-insensitive 22Na influx was deeply inhibited by bumetanide. 22Na influx was dependent on the presence of extracellular K+ and Cl–. Since Na-K-Cl activity dramatically decreased with time in culture, further characterization of the cotransport on polarized cells could not be performed. The phorbol ester PMA inhibited Na-K-Cl cotransport in a time-and concentration-dependent manner. This inhibition was mimicked by oleoylacetylglycerol, dioctanoylglycerol, and the diacylglycerol kinase inhibitor R59022, and was reversed by an antagonist of PKC, staurosporine. Since the Na-K-Cl cotransport has been reported to be involved in cell volume regulation, we investigated its modulation by changes in extracellular osmolarity. Na-K-Cl activity was increased after a two-step procedure: swelling in hypotonic medium followed by shrinking in hypertonic medium. Under these conditions, cotransport activity increased whenever PKC activity was up-or downregulated, which suggests that the cell volume-induced modulation of the cotransport is independent from the PKC activity. Though we were not able to determine the polarity of the cotransport, it may also be involved in the absorptive function of alveolar type II cells, and would provide an alternate pathway for sodium entry.This work was supported by grants from INSERM, CNRS, Université Denis Diderot Paris 7, Faculté Xavier Bichat, Fondation pour la Recherche Médicale, and Laboratoire de Recherches Physiologiques. 相似文献
89.
90.
Rat hepatoma (HTC) cell 6-phosphofructo-2-kinase differs from that in liver and can be separated from fructose-2,6-bisphosphatase 总被引:4,自引:0,他引:4
A M Loiseau M H Rider D Foret G G Rousseau L Hue 《European journal of biochemistry》1988,175(1):27-32
6-Phosphofructo-2-kinase was purified from rat liver and hepatoma (HTC) cells. The HTC cell enzyme had kinetic properties different from those of the liver enzyme (more sensitive to inhibition by citrate and not inhibited by sn-glycerol 3-phosphate) and was not a substrate of the cyclic-AMP-dependent protein kinase. Unlike the liver enzyme, which is bifunctional and phosphorylated by fructose 2,6-[2-32P]bisphosphate, the HTC cell enzyme contained no detectable fructose-2,6-bisphosphatase activity and phosphorylation by fructose 2,6-[2-32P]-bisphosphate could not be detected. HTC cell fructose-2,6-bisphosphatase could be separated from 6-phosphofructo-2-kinase activity by purification. Antibodies raised against liver 6-phosphofructo-2-kinase did not precipitate HTC cell fructose-2,6-bisphosphatase whose kinetic properties were completely different from those of the liver enzyme. 相似文献