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1.
As the cellular slime mold, Dictyostelium discoideum, undergoes development, a phospholipid fraction containing 80% N-acylethanolamine glycerophospholipids (NAEGPs) and 20% acylphosphatidylglycerol (APG) disappears during the aggregation stage. In this study, the subcellular distribution of that NAEGP phospholipid fraction and the precise time period of disappearance of the fraction were determined. The content of the NAEGP fraction was determined in aggregating cells at 2-h intervals from the beginning of the developmental phase through 14 h, when the cells were completely aggregated. The NAEGP fraction comprised about 8% of the phospholipids in amoebae just starting the development cycle and about 12% in cells between 2 and 6 h of development; then its level decreased until it could not be detected at 12 and 14 h of development. The mole percentage of the total lipid phosphate in the NAEGP fraction was determined in isolated subcellular organelles. The phagolysosomes were enriched in the NAEGP fraction 1.7-2-fold over the level found in the amoebae and about 8-fold over the level in fractions highly enriched in the plasma membrane, mitochondria or peroxisomes. The content of phagolysosomes was determined by electron microscopy of aggregating cells. The amoebae contained large amounts of phagolysosomes up to 6 h of development, and then they gradually disappeared between 6 and 12 h of development. This combination of quantitative phospholipid analysis, subcellular organelle isolation and electron microscopy has revealed that in D. discoideum amoebae, the phagolysosomes were selectively enriched in the NAEGP fraction and both the NAEGP-enriched phagolysosomes and the NAEGPs disappeared concurrently between 6 and 12 h of development.  相似文献   
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Biomechanics and Modeling in Mechanobiology - The human lumbar facet capsule, with the facet capsular ligament (FCL) that forms its primary constituent, is a common source of lower back pain. Prior...  相似文献   
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Background  

a decline in immune and endocrine function occurs with aging. The main purpose of this study was to investigate the impact of long-term endurance training on the immune and endocrine system of elderly men. The possible interaction between these systems was also analysed.  相似文献   
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  总被引:8,自引:0,他引:8  
We have examined the phylogenetic distribution of two t-specific markersamong representatives of various taxa belonging to the genus Mus. Thecentromeric TCP-1a marker (a testicular protein variant specific for allt-haplotypes so far studied) has also been apparently detected in severalnon-t representatives of the Mus IVA, Mus IVB, and probably M. cervicolorspecies. By contrast, a t-specific restriction- fragment-lengthpolymorphism allele (RFLP) of the telomeric alpha- globin pseudogene DNAmarker alpha-psi-4 was found only in animals belonging to the M.musculus-complex species either bearing genuine t- haplotypes or, like theM. m. bactrianus specimen studied here, likely to do so. This t-specificalpha-psi-4 RFLP allele was found to be as divergent from the RFLP allelesof the latter, non-t, taxonomical groups as it is from Mus 4A, Mus 4B, orM. spretus ones. These results suggest the presence of t-haplotypes and oft-specific markers in populations other than those belonging to the M. m.domesticus and M. m. musculus subspecies, implying a possible origin fort-haplotypes prior to the radiation of the most recent offshoot of the Musgenus (i.e., the spretus/domesticus divergence), some 1-3 Myr ago.  相似文献   
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Substitute methadone prescribing is one of the main modes of treatment for opiate dependence. This study examined the relationship between methadone dose (measured by daily dose and methadone's active (R)‐enantiomer blood levels) and opiate receptor function. Nine subjects on substitute methadone (30‐90 mg daily) received three subcutaneous injections 1.5 hours apart (saline, 5 mg and 10 mg hydromorphone, a short‐acting opiate agonist) followed by measures of functional response in particular saccadic eye movements (SEMs), as well as self‐report measures. Ten mg of hydromorphone significantly slowed SEM parameters (peak velocity by 15%, p <0.005; peak acceleration by 20%, p <0.025; peak deceleration by 26%, p <0.025) and the SEM velocity changes correlated significantly with (R)‐methadone levels (r =0.844, p <0.005) and with the oral dose of methadone being taken (r =0.829, p <0.005). Although a similar trend was observed for 5 mg, this was not significant. These finding suggest that, at higher methadone doses (resulting in higher plasma concentrations), there is significant tolerance to the action of agonists. Such studies may help in refining our understanding of the actions of methadone and the SEM measure could help in defining the degree of tolerance in individuals using street heroin.  相似文献   
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  总被引:3,自引:1,他引:3  
The results described in the accompanying article support the model inwhich glucosylphosphoryldolichol (Glc-P-Dol) is synthesized on thecytoplasmic face of the ER, and functions as a glucosyl donor for threeGlc-P-Dol:Glc0-2Man9-GlcNAc2-P-P-Dol glucosyltransferases (GlcTases) in thelumenal compartment. In this study, the enzymatic synthesis and structuralcharacterization by NMR and electrospray-ionization tandem massspectrometry of a series of water-soluble beta-Glc-P-Dol analogs containing2-4 isoprene units with either the cis - or trans - stereoconfiguration inthe beta-position are described. The water- soluble analogs were (1) usedto examine the stereospecificity of the Glc-P-Dol:Glc0-2Man9GlcNAc2-P-P-Dolglucosyltransferases (GlcTases) and (2) tested as potential substrates fora membrane protein(s) mediating the transbilayer movement of Glc-P-Dol insealed ER vesicles from rat liver and pig brain. The Glc-P-Dol-mediatedGlcTases in pig brain microsomes utilized [3H]Glc-labeled Glc-P-Dol10,Glc-P-(omega, c )Dol15, Glc-P(omega, t,t )Dol20, and Glc-P-(omega, t,c)Dol20as glucosyl donors with [3H]Glc3Man9GlcNAc2-P-P-Dol the major productlabeled in vitro. A preference was exhibited for C15-20 substratescontaining an internal cis -isoprene unit in the beta-position. Inaddition, the water-soluble analog, Glc-P-Dol10, was shown to enter thelumenal compartment of sealed microsomal vesicles from rat liver and pigbrain via a protein-mediated transport system enriched in the ER. Theproperties of the ER transport system have been characterized. Glc-P-Dol10was not transported into or adsorbed by synthetic PC-liposomes orbovine erythrocytes. The results of these studies indicate that (1) theinternal cis -isoprene units are important for the utilization of Glc-P-Dolas a glucosyl donor and (2) the transport of the water- soluble analog mayprovide an experimental approach to assay the hypothetical \"flippase\"proposed to mediate the transbilayer movement of Glc-P-Dol from thecytoplasmic face of the ER to the lumenal monolayer.  相似文献   
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Polypharmacology, the ability of drugs to interact with multiple targets, is a fundamental concept of interest to the pharmaceutical industry in its efforts to solve the current issues of the rise in the cost of drug development and decline in productivity. Polypharmacology has the potential to greatly benefit drug repurposing, bringing existing pharmaceuticals on the market to treat different ailments quicker and more affordably than developing new drugs, and may also facilitate the development of new, potent pharmaceuticals with reduced negative off-target effects and adverse side effects. Present day computational power, when combined with applications such as supercomputer-based virtual high-throughput screening (docking) will enable these advances on a massive chemogenomic level, potentially transforming the pharmaceutical industry. However, while the potential of supercomputing-based drug discovery is unequivocal, the technical and fundamental challenges are considerable.  相似文献   
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Cell aggregates of Dictyostelium discoideum can either construct fruiting bodies directly at the site of aggregation or transform into migrating slugs and move away. The latter can be induced at any time by appropriate environmental signals to stop migrating and construct fruits. In this and a previous publication (P. C. Newelland M. Sussman, J. Mol. Biol., 49 (1970)627), the patterns of accumulation and disapperance of three enzymes have been examined during these alternative developmental programs. The enzymes are: UDP-glucose pyrophosphorylase (EC 2.7.7.9), UDP-galactose 4-epimerase (EC 5.1.3.2), and UDP-galactose : polysaccharide galactosyl-transferase. The results indicate that:
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1. The performances of all three enzymes differ drastically but consistently in these two developmental modes in respect to times at which the activities begin to accumulate, the periods of accumulation, and the periods of disappearance. There is no evidence that the three are coordinately controlled with respect to any of the above.  相似文献   
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