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1.
Homeostatic mechanisms regulate synaptic function to maintain nerve and muscle excitation within reasonable physiological limits. The mechanisms that initiate homeostasic changes to synaptic function are not known. We specifically impaired cellular depolarization by expressing the Kir2.1 potassium channel in Drosophila muscle. In Kir2.1-expressing muscle there is a persistent outward potassium current ( approximately 10 nA), decreased muscle input resistance (50-fold), and a hyperpolarized resting potential. Despite impaired muscle excitability, synaptic depolarization of muscle achieves wild-type levels. A quantal analysis demonstrates that increased presynaptic release (quantal content), without a change in quantal size (mEPSC amplitude), compensates for altered muscle excitation. Because morphological synaptic growth is normal, we conclude that a homeostatic increase in presynaptic release compensates for impaired muscle excitability. These data demonstrate that a monitor of muscle membrane depolarization is sufficient to initiate synaptic homeostatic compensation. 相似文献
2.
P Paradis J L Rouleau H Shenasa L Brakier-Gingras 《Canadian journal of physiology and pharmacology》1989,67(3):197-201
Congestive heart failure was induced in rabbits by a chronic treatment with a low dose of adriamycin (0.75 mg/kg intravenously 3 times per week for 11 weeks). Twenty-four to 48 h after the last injection, adriamycin-treated rabbits had a three-fold increase in plasma norepinephrine, a seven-fold increase in plasma epinephrine, a 19 +/- 8% increase in heart rate, and a 54 +/- 10% decrease in the total tension generated by their isolated papillary muscles, when compared with normal age-matched controls. This demonstrated the occurrence of the cardiomyopathy and heart failure. The effect of adriamycin on myocardial and diaphragmatic protein synthesis was examined in vivo after a 1-h infusion with [3H]leucine and in vitro after a 2-h incubation of right ventricular papillary muscle with [3H]leucine. The rate of in vivo [3H]leucine incorporation into total protein was increased in the heart of the adriamycin-treated rabbits. The increases were 60 +/- 16% in the left ventricle, 49 +/- 18% in the septum, 32 +/- 18% in the right ventricle, and 66 +/- 16% in the atria. A similar increase was observed when measuring the rate of [3H]leucine incorporation into myosin, a myofibrillar protein, and when the rate of [3H]leucine incorporation into total protein was measured in vitro in papillary muscle. In contrast, the rate of [3H]leucine incorporation into total protein of the diaphragm was not significantly changed.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
3.
Linkage analysis was performed in a family with nonspecific X-linked mental retardation (MRX). Affected individuals had no clinical characteristics other than mental retardation. Linkage was detected to the marker loci DXS477, DXS465, DXS52, DXS15 and F8C with maximum lod scores of 1.70, 1.32, 2.52, 1.70, and 1.09, respectively ( = 0.0). The results strongly indicate that the gene for mental retardation in the family studied maps close to DXS52. 相似文献
4.
Increased preproenkephalin A gene expression in the rat heart after induction of a myocardial infarction. 总被引:1,自引:0,他引:1
P Paradis M Dumont P Bélichard J L Rouleau S Lemaire L Brakier-Gingras 《Biochimie et biologie cellulaire》1992,70(7):593-598
The expression of preproenkephalin A (ppENK) gene was investigated in the rat heart, following the onset of myocardial infarction induced by ligation of the left anterior descending coronary artery. The relative abundance of ppENK mRNA and the level of enkephalins were measured by Northern blot analysis and radioimmunoassay, respectively, in the ventricles from control-unoperated, sham-operated, and operated rats. Three hours after the surgery, a comparison between rats with infarction and sham-operated rats revealed that the relative abundance of ppENK mRNA and the level of enkephalins were increased three- to four- and two- to three-fold, respectively, in the ventricles of rats with infarction. No difference was observed between rats with infarction and sham-operated rats 24 h after the surgery, or between rats with infarction compared at time intervals of 3 and 24 h following the surgery. The abundance of the ppENK mRNA in the polysomal fraction of the ventricular septum was also measured 3 h after the surgery and found to be threefold higher in rats with infarction as compared with sham-operated rats. These results indicate that the level of enkephalins rapidly increases in the ventricles of rats following myocardial infarction, and that this higher level may be ascribed to a stimulation of the local synthesis of enkephalins. 相似文献
5.
Amira Azizan Stefano Anile Clayton K. Nielsen Emmanuel Paradis Sébastien Devillard 《Global Ecology and Biogeography》2023,32(10):1858-1869
Aim
Insights into the biological and evolutionary traits of species, and their ability to cope with global changes, can be gained by studying genetic diversity within species. A cornerstone hypothesis in evolutionary and conservation biology suggests that genetic diversity decreases with decreasing population size, however, population size is difficult to estimate in threatened species with large distribution ranges, and evidence for this is limited to few species. To address this gap, we tested this hypothesis across multiple closely related species at a global scale using population density which is a more accessible measure.Location
Global.Time Period
Contemporary.Major Taxa Studied
Wild felids in their natural habitats.Methods
We obtained data from published estimates of population density assessed via camera trap and within-population genetic diversity generated from microsatellite markers on 18 felid species across 41 countries from 354 studies. We propose a novel method to standardize population density estimates and to spatially join data using K-means clustering. Linear mixed-effect modelling was applied to account for confounding factors such as body mass, generation length and sample size used for the genetic estimates.Results
We found a significant positive correlation between population density and genetic diversity, particularly observed heterozygosity and allelic richness. While the confounding factors did not affect the main results, long generation length and large sample size were significantly associated with high genetic diversity. Body mass had no effect on genetic diversity, likely because large-bodied species were over-represented in our data sets.Main Conclusions
Our study emphasizes how recent demographic processes shape neutral genetic diversity in threatened and small populations where extinction vortex is a risk. Although caution is needed when interpreting the small population density effect in our findings, our methodological framework shows promising potential to identify which populations require actions to conserve maximal genetic variation. 相似文献6.
The gene for the purine salvage enzyme hypoxanthine phosphoribosyltransferase (HPRT) is expressed at a low level in many cells. As is the case with several other “housekeeping genes,” thorough studies of hprt gene regulation have been hampered by the low levels of its mRNA. We have used RNA/RNA hybridization in solution to determine the concentration of hprt-RNA in human cells. The sensitivity and specificity of the method have been validated, and it is shown that hprt-RNA can be accurately determined at a level of a few mRNA molecules per cell. As expected for a housekeeping gene, low and relatively constant hprt-RNA levels (0.3–0.8 pg/μg DNA) were found in primary cultures of normal amnion cells and fibroblasts, EBV-transformed lymphoblastoid cell lines, neuroblastoma, glioblastoma, and melanoma cell cultures. While resting lymphocytes were found to contain very low amounts of hprt-RNA, lymphocytes stimulated with phytohemagglutinin (PHA) showed a 10-fold increase to about 0.8–1.2 pg/μg DNA, which corresponds to 6–10 hprt-RNA molecules per cell. The level started to increase about 20 h after PHA stimulation, 5–10 h before the onset of DNA synthesis, and a steady-state level was reached after 2–3 days in culture. In PHA-stimulated lymphocytes from two brothers with inherited HPRT deficiency (LeschNyhans syndrome), the hprt-RNA level in PHA-stimulated lymphocytes was only about 25% of that in normal subjects. In T-cells selected for HPRT deficiency by growth in 6-thioguanine medium, the levels of hprt-RNA were either normal or very low, which probably reflects the different nature of the mutations involved. These results demonstrate the sensitivity of this method for determinations of low levels of RNA and clearly show induction of hprt-RNA after mitogenic stimulation of human lymphocytes. 相似文献
7.
K Paradis A Weber E G Seidman J Larochelle L Garel C Lenaerts C C Roy 《American journal of human genetics》1990,47(2):338-342
Sixteen tyrosinemic patients were evaluated in our institution for a possible liver transplantation. All patients showed biochemical and/or radiological evidence of liver dysfunction. Renal involvement was found to be more abnormal than expected. Seven patients have been transplanted, with two patients receiving a combined liver-kidney transplant. Hepatocarcinoma was detected in two of eight patients in whom the whole liver was examined. Six (37.5%) of the initial 16 patients have died since evaluation, one of the six dying after combined liver-kidney transplantation. Posttransplantation survival was 86%, with normal liver function, normal growth, and no recurrence of neurological crises on a normal diet. 相似文献
8.
Yves Paradis Marc Pépino Simon Bernatchez Denis Fournier Léon L’Italien Jérôme Doucet-Caron 《Zeitschrift fur angewandte Ichthyologie》2021,37(5):664-676
Movement of Atlantic sturgeon (Acipenser oxyrinchus oxyrinchus) and lake sturgeon (A. fulvescens) in the St. Lawrence Estuary (Québec, Canada) are not fully understood. To assess the movement extent of both species, a mark–recapture study was conducted in collaboration with commercial fishermen operating in the St. Lawrence Estuary. Between 1981 and 2015, 3,367 Atlantic sturgeon (fork length 21.8–199.5 cm) and 3,180 lake sturgeon (fork length 17.8–190.8 cm) were tagged and released. Of these, 673 Atlantic sturgeon and 42 lake sturgeon were recaptured. The maximum distances traveled between capture and recapture locations were 1,307 km for Atlantic sturgeon (8 years after initial capture) and 252 km for lake sturgeon (less than 1 year after initial capture). Statistical analyses identified differences in the dispersal distance of both species as revealed by a first component characterized by individuals with short dispersal distances (98% and <35 km for Atlantic sturgeon; 58% and <1 km for lake sturgeon) and a second component characterized by individuals with longer dispersal distances (2% and >600 km for Atlantic sturgeon; 42% and >190 km for lake sturgeon). We suggest that the short dispersal distances detected in the vast majority of Atlantic sturgeon recaptures likely reflect strong site fidelity, highlighting the importance of the St. Lawrence Estuary as a preferred habitat for juveniles and subadults. Although recaptures were low for lake sturgeon because this species is only marginally targeted by commercial fishermen in the St. Lawrence Estuary, our results also showed that this species uses estuarine habitats and that half of the population seems to exhibit strong site fidelity (67% of individuals were recaptured within 2 km). 相似文献
9.
Katherine R. Bull Andrew J. Rimmer Owen M. Siggs Lisa A. Miosge Carla M. Roots Anselm Enders Edward M. Bertram Tanya L. Crockford Belinda Whittle Paul K. Potter Michelle M. Simon Ann-Marie Mallon Steve D. M. Brown Bruce Beutler Christopher C. Goodnow Gerton Lunter Richard J. Cornall 《PLoS genetics》2013,9(1)
Forward genetics screens with N-ethyl-N-nitrosourea (ENU) provide a powerful way to illuminate gene function and generate mouse models of human disease; however, the identification of causative mutations remains a limiting step. Current strategies depend on conventional mapping, so the propagation of affected mice requires non-lethal screens; accurate tracking of phenotypes through pedigrees is complex and uncertain; out-crossing can introduce unexpected modifiers; and Sanger sequencing of candidate genes is inefficient. Here we show how these problems can be efficiently overcome using whole-genome sequencing (WGS) to detect the ENU mutations and then identify regions that are identical by descent (IBD) in multiple affected mice. In this strategy, we use a modification of the Lander-Green algorithm to isolate causative recessive and dominant mutations, even at low coverage, on a pure strain background. Analysis of the IBD regions also allows us to calculate the ENU mutation rate (1.54 mutations per Mb) and to model future strategies for genetic screens in mice. The introduction of this approach will accelerate the discovery of causal variants, permit broader and more informative lethal screens to be used, reduce animal costs, and herald a new era for ENU mutagenesis. 相似文献
10.
Kristin E Svensson Marianne I Velandia Ann-Sofi T Matthiesen Barbara L Welles-Nyström Ann-Marie E Widström 《International breastfeeding journal》2013,8(1):1-13