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  总被引:5,自引:1,他引:5  
Immunoglobulins are encoded by a large multigene system that undergoessomatic rearrangement and additional genetic change during the developmentof immunoglobulin-producing cells. Inducible antibody and antibody-likeresponses are found in all vertebrates. However, immunoglobulin possessingdisulfide-bonded heavy and light chains and domain-type organization hasbeen described only in representatives of the jawed vertebrates. Highdegrees of nucleotide and predicted amino acid sequence identity areevident when the segmental elements that constitute the immunoglobulin geneloci in phylogenetically divergent vertebrates are compared. However, theorganization of gene loci and the manner in which the independent elementsrecombine (and diversify) vary markedly among different taxa. One strikingpattern of gene organization is the \"cluster type\" that appears to berestricted to the chondrichthyes (cartilaginous fishes) and limitssegmental rearrangement to closely linked elements. This type of geneorganization is associated with both heavy- and light-chain gene loci. Insome cases, the clusters are \"joined\" or \"partially joined\" in the germline, in effect predetermining or partially predetermining, respectively,the encoded specificities (the assumption being that these are expressed)of the individual loci. By relating the sequences of transcribed geneproducts to their respective germ-line genes, it is evident that, in somecases, joined-type genes are expressed. This raises a question about theexistence and/or nature of allelic exclusion in these species. Theextensive variation in gene organization found throughout the vertebratespecies may relate directly to the role of intersegmental(V<==>D<==>J) distances in the commitment of the individualantibody-producing cell to a particular genetic specificity. Thus, theevolution of this locus, perhaps more so than that of others, may reflectthe interrelationships between genetic organization and function.  相似文献   
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In both yellow perch ( Perca flavescens ) and walleye ( Stizostedion vitreum ), females grow significantly faster and reach a larger ultimate size than males. In addition, reproductive development in both of these species can have a significant negative impact on somatic growth and fillet yield. Accordingly, methods for producing monosex female populations and for inducing sterility, have important potential applications for both commercial fish culture and fisheries management. Of the several available methods for producing monosex female populations in fishes (such as yellow perch and walleye) in which females are homogametic, the preferred method (described herein) may be to treat juveniles with androgens to induce phenotypic sex inversion of genetic females, and to subsequently use sperm from these females to fertilize normal eggs. Initial efforts at inducing sterility focused on the direct use of either heat or hydrostatic pressure shocks to produce triploid yellow perch and walleye. The gonadal development of triploid yellow perch and walleye of both sexes is retarded compared to that of diploids, and triploid yellow perch can have higher fillet yields than diploids. The direct use of heat and pressure shocks to induce triploidy in yellow perch, however, has negative effects on growth that are independent of ploidy status. One way to circumvent this problem is to produce triploids by crossing fertile tetraploids with diploids. To date, methods of producing viable tetraploids (beyond the larval stage) have been developed for yellow perch but not for walleye.  相似文献   
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Tyrosine kinases are important regulators of synaptic strength. Here, we describe a key component of the synaptic vesicle release machinery, Munc18‐1, as a phosphorylation target for neuronal Src family kinases (SFKs). Phosphomimetic Y473D mutation of a SFK phosphorylation site previously identified by brain phospho‐proteomics abolished the stimulatory effect of Munc18‐1 on SNARE complex formation (“SNARE‐templating”) and membrane fusion in vitro. Furthermore, priming but not docking of synaptic vesicles was disrupted in hippocampal munc18‐1‐null neurons expressing Munc18‐1Y473D. Synaptic transmission was temporarily restored by high‐frequency stimulation, as well as by a Munc18‐1 mutation that results in helix 12 extension, a critical conformational step in vesicle priming. On the other hand, expression of non‐phosphorylatable Munc18‐1 supported normal synaptic transmission. We propose that SFK‐dependent Munc18‐1 phosphorylation may constitute a potent, previously unknown mechanism to shut down synaptic transmission, via direct occlusion of a Synaptobrevin/VAMP2 binding groove and subsequent hindrance of conformational changes in domain 3a responsible for vesicle priming. This would strongly interfere with the essential post‐docking SNARE‐templating role of Munc18‐1, resulting in a largely abolished pool of releasable synaptic vesicles.  相似文献   
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The walleye ( Stizostedion vitreum ) is a North American mesothermal freshwater teleost that spawns once each year in early spring. Walleye spawn randomly over suitable substrates and do not provide any parental protection for eggs or juveniles. The majority of gonadal recrudescence in adult male walleye occurs in the autumn, and walleye testes contain large numbers of viable spermatozoa from late autumn through the spawning season. Adult female walleye exhibit group synchronous ovarian development, and similar to males, the majority of gonadal development occurs in the autumn. Evidence suggests that 17α,20β-dihydroxyprogesterone is the maturational steroid in this species. Simple environmental manipulations coupled with injections of human chorionic gonadotropin can be used to advance spawning in walleye by up to 12 weeks. To spawn and propagate walleye, hatcheries in North America use a wide range of methods that have been developed to meet the needs and conditions present at specific facilities.  相似文献   
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Dopamine-beta-hydroxylase (D beta H) catalyzes the conversion of dopamine to norepinephrine and is released from sympathetic neurons into the circulation. Plasma-D beta H activity varies widely between individuals, and a subgroup of the population has very low activity levels. Mounting evidence suggests that the DBH structural gene is itself the major quantitative-trait locus (QTL) for plasma-D beta H activity, and a single unidentified polymorphism may account for a majority of the variation in activity levels. Through use of both sequencing-based mutational analysis of extreme phenotypes and genotype/phenotype correlations in samples from African American, European American (EA), and Japanese populations, we have identified a novel polymorphism (--1021C-->T), in the 5' flanking region of the DBH gene, that accounts for 35%--52% of the variation in plasma-D beta H activity in these populations. In EAs, homozygosity at the T allele predicted the very low D beta H-activity trait, and activity values in heterozygotes formed an intermediate distribution, indicating codominant inheritance. Our findings demonstrate that --1021C-->T is a major genetic marker for plasma-D beta H activity and provide new tools for investigation of the role of both D beta H and the DBH gene in human disease.  相似文献   
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Cells react to their microenvironment by integrating external stimuli into phenotypic decisions via an intracellular signaling network. To analyze the interplay of environment, local neighborhood, and internal cell state effects on phenotypic variability, we developed an experimental approach that enables multiplexed mass cytometric imaging analysis of up to 240 pooled spheroid microtissues. We quantified the contributions of environment, neighborhood, and intracellular state to marker variability in single cells of the spheroids. A linear model explained on average more than half of the variability of 34 markers across four cell lines and six growth conditions. The contributions of cell‐intrinsic and environmental factors to marker variability are hierarchically interdependent, a finding that we propose has general implications for systems‐level studies of single‐cell phenotypic variability. By the overexpression of 51 signaling protein constructs in subsets of cells, we also identified proteins that have cell‐intrinsic and cell‐extrinsic effects. Our study deconvolves factors influencing cellular phenotype in a 3D tissue and provides a scalable experimental system, analytical principles, and rich multiplexed imaging datasets for future studies.  相似文献   
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Lee  YC; Kawasaki  N; Lee  RT; Suzuki  N 《Glycobiology》1998,8(9):849-856
Quantum dye (QD), a macrocyclic europium-chelate, developed as a cytological marker, has never been used for quantitative applications. It would be ideal, however, if the same tracer can be used for both qualitative and quantitative purposes. We have labeled some lectins and neoglycoproteins with QD for the purpose of quantitative analyses in glycobiology, and tested its suitability in three different areas in glycobiology: (1) glycosyltransferase, (2) an animal lectin - mannose- binding protein, and (3) the Gal/GalNAc receptor of rat liver membrane. Usefulness of QD-labeled lectins was amply demonstrated by the quantification of galactosyltransferase activity using QD-soybean agglutinin and QD-RCA120 ( Ricinus communis agglutinin). We also showed that QD-labeled neoglycoproteins, QD-Man-BSA and QD-Gal-BSA, can replace radioiodinated counterparts in the binding assays of animal lectins (serum mannose binding protein and hepatic Gal/GalNAc receptor.) The advantage of QD and other europium labels is that it does not decay as radioiodides do. The long shelf-life results in more consistent results from repeated experiments.   相似文献   
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