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91.
Iness Charfi Khaled Abdallah Louis Gendron Graciela Pineyro 《Cellular and molecular life sciences : CMLS》2018,75(12):2257-2271
Soon after internalization delta opioid receptors (DOPrs) are committed to the degradation path by G protein-coupled receptor (GPCR)-associated binding protein. Here we provide evidence that this classical post-endocytic itinerary may be rectified by downstream sorting decisions which allow DOPrs to regain to the membrane after having reached late endosomes (LE). The LE sorting mechanism involved ESCRT accessory protein Alix and the TIP47/Rab9 retrieval complex which supported translocation of the receptor to the TGN, from where it subsequently regained the cell membrane. Preventing DOPrs from completing this itinerary precipitated acute analgesic tolerance to the agonist DPDPE, supporting the relevance of this recycling path in maintaining the analgesic response by this receptor. Taken together, these findings reveal a post-endocytic itinerary where GPCRs that have been sorted for degradation can still recycle to the membrane. 相似文献
92.
Ryan T. Kendall Louis M. Luttrell 《Cellular and molecular life sciences : CMLS》2009,66(18):2953-2973
The termination of heptahelical receptor signaling is a multilevel process coordinated, in large part, by members of the arrestin
family of proteins. Arrestin binding to agonist-occupied receptors promotes desensitization by interrupting receptor-G protein
coupling, while simultaneously recruiting machinery for receptor endocytosis, vesicular trafficking, and receptor fate determination.
By simultaneously binding other proteins, arrestins also act as ligand-regulated scaffolds that recruit protein and lipid
kinase, phosphatase, phosphodiesterase, and ubiquitin ligase activity into receptor-based multiprotein ‘signalsome’ complexes.
Arrestin-binding thus ‘switches’ receptors from a transient G protein-coupled state to a persistent arrestin-coupled state
that continues to signal as the receptor transits intracellular compartments. While it is clear that signalsome assembly has
profound effects on the duration and spatial characteristics of heptahelical receptor signals, the physiologic functions of
this novel signaling mechanism are poorly understood. Growing evidence suggests that signalsomes regulate such diverse processes
as endocytosis and exocytosis, cell migration, survival, and contractility. 相似文献
93.
Geothermal energy potential is usually discussed in the context of conventional or engi-neered systems and at the scale of an individual reservoir. Whereas exploration for conventional reser-voirs has ... 相似文献
94.
Buoyancy exchange between the deep and the upper ocean, which is essential for maintaining global ocean circulation, mainly occurs through turbulent mixing. This mixing is thought to result primarily from instability of the oceanic internal wave field, but internal waves tend to radiate energy away from the regions in which they are generated rather than dissipate it locally as turbulence and the resulting distribution of turbulent mixing remains unknown. Another, more direct, mixing mechanism involves the generation of turbulence as strong flows pass through narrow passages in topography, but the amount of turbulence generated at such locations remains poorly quantified owing to a lack of direct measurements. Here we present observations from the crest of the Mid-Atlantic Ridge in the subtropical North Atlantic Ocean that suggest that passages in rift valleys and ridge-flank canyons provide the most energetic sites for oceanic turbulence. Our measurements show that diffusivities as large as 0.03 m2 s(-1) characterize the mixing downstream of a sill in a well-stratified boundary layer, with mixing levels remaining of the order of 10(-4) m2 s(-1) at the base of the main thermocline. These mixing rates are significantly higher than the diffusivities of the order of 10(-5) m2 s(-1) that characterize much of the global thermocline and the abyssal ocean. Our estimates suggest that overflows associated with narrow passages on the Mid-Atlantic Ridge in the North Atlantic Ocean produce as much buoyancy flux as has previously been estimated for the entire Romanche fracture zone, a large strait in the Mid-Atlantic Ridge that connects the North and South Atlantic basins. This flux is equivalent to the interior mixing that occurs in the entire North Atlantic basin at the depth of the passages, suggesting that turbulence generated in narrow passages on mid-ocean ridges may be important for buoyancy flux at the global scale. 相似文献
95.
Louis Glangeaud 《Cellular and molecular life sciences : CMLS》1947,3(2):58-69
Sans résumé 相似文献
96.
Padiath QS Saigoh K Schiffmann R Asahara H Yamada T Koeppen A Hogan K Ptácek LJ Fu YH 《Nature genetics》2006,38(10):1114-1123
Adult-onset autosomal dominant leukodystrophy (ADLD) is a slowly progressive neurological disorder characterized by symmetrical widespread myelin loss in the central nervous system, with a phenotype similar to chronic progressive multiple sclerosis. In this study, we identify a genomic duplication that causes ADLD. Affected individuals carry an extra copy of the gene for the nuclear laminar protein lamin B1, resulting in increased gene dosage in brain tissue from individuals with ADLD. Increased expression of lamin B1 in Drosophila melanogaster resulted in a degenerative phenotype. In addition, an abnormal nuclear morphology was apparent when cultured cells overexpressed this protein. This is the first human disease attributable to mutations in the gene encoding lamin B1. Antibodies to lamin B are found in individuals with autoimmune diseases, and it is also an antigen recognized by a monoclonal antibody raised against plaques from brains of individuals with multiple sclerosis. This raises the possibility that lamin B may be a link to the autoimmune attack that occurs in multiple sclerosis. 相似文献
97.
98.
Yang J Manolio TA Pasquale LR Boerwinkle E Caporaso N Cunningham JM de Andrade M Feenstra B Feingold E Hayes MG Hill WG Landi MT Alonso A Lettre G Lin P Ling H Lowe W Mathias RA Melbye M Pugh E Cornelis MC Weir BS Goddard ME Visscher PM 《Nature genetics》2011,43(6):519-525
We estimate and partition genetic variation for height, body mass index (BMI), von Willebrand factor and QT interval (QTi) using 586,898 SNPs genotyped on 11,586 unrelated individuals. We estimate that ~45%, ~17%, ~25% and ~21% of the variance in height, BMI, von Willebrand factor and QTi, respectively, can be explained by all autosomal SNPs and a further ~0.5-1% can be explained by X chromosome SNPs. We show that the variance explained by each chromosome is proportional to its length, and that SNPs in or near genes explain more variation than SNPs between genes. We propose a new approach to estimate variation due to cryptic relatedness and population stratification. Our results provide further evidence that a substantial proportion of heritability is captured by common SNPs, that height, BMI and QTi are highly polygenic traits, and that the additive variation explained by a part of the genome is approximately proportional to the total length of DNA contained within genes therein. 相似文献
99.
100.
J Y Detaille C G Caillard S Mondot J C Louis L Julou 《Comptes rendus des séances de l'Académie des sciences. Série D, Sciences naturelles》1979,288(5):555-558
In the Dog, 3-(2-hydroxy-3 isopropylamino-proxy)-2-phenyl-1-isoindolinone (RS, SR) possesses an anti-arrhythmic activity similar to that of quinidine but at dose levels 2 to 6 times lower than in the case of the latter compound. Furthermore, in contrast to quinidine, at the dose levels where the antiarrhythmic activity is well observed, the compound is devoid of hypotensive activity and of depressive action on cardiac contractility. The first clinical studies of this compound have shown its usefulness in the treatment of ventricular and supraventricular arrhythmias. 相似文献