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31.
Hereditary spherocytosis (HS) is a common, clinically heterogeneous haemolytic anaemia in which the primary erythrocyte defect is believed to be some abnormality in the spectrin-actin membrane skeleton, leading to loss of surface membrane. Recessively inherited spectrin deficiency with extreme erythrocyte fragility and spherocytosis has been identified in certain mutant mice and two severely anaemic humans. Although suspected, deficiency of spectrin has not been demonstrated in less severe forms of human HS. We not report the quantitation of erythrocytes spectrin by radioimmunoassay. We found that normal erythrocytes contained 240,000 copies of spectrin heterodimer, whereas erythrocytes from 14 patients with a variety of types of HS were all partially deficient in spectrin (range 74,000-200,000 copies), the magnitude of the deficiency correlating with the severity of the disease. Spectrin deficiency of varying degrees is common in HS and probably represents the principal structural defect leading to loss of surface membrane. 相似文献
32.
Synapsin I is a microtubule-bundling protein 总被引:18,自引:0,他引:18
Synapsin I, a synaptic vesicle protein, is thought to be involved in the regulation of neurotransmission through its phosphorylation by the cyclic AMP-dependent and Ca2+/calmodulin-dependent protein kinases which become activated upon depolarization of nerve endings. However, despite its recent characterization as a spectrin-binding protein immunologically related to erythrocyte protein 4.1, other interactions of synapsin I with structural proteins remain unknown. We report here that synapsin I can co-cycle with microtubules through three cycles of warm polymerization and cold depolymerization. Synapsin I binds saturably to microtubules stabilized by taxol, with an estimated dissociation constant (Kd) of 4.5 microM and a stoichiometry of 1.2 mol of synapsin binding sites per mol tubulin dimer. Synapsin I also increases the turbidity of tubulin solutions at 37 degrees C, but without causing detectable alterations in the critical concentration required for polymerization. Mixtures of synapsin I and tubulin observed by negative stain electron microscopy contain bundles of microtubules, accounting for the effect of synapsin I on tubulin turbidity. Synapsin I is thus a candidate to mediate or regulate the interaction of synaptic vesicles with microtubules. 相似文献
33.
Molecular cloning and complete amino-acid sequence of form-I phosphoinositide-specific phospholipase C 总被引:20,自引:0,他引:20
We report the molecular cloning and sequence of a phosphoinositide-specific phospholipase C (PI-PLC), an enzyme that is of particular interest because of its central role in cell signal transduction. The signals in question are those delivered by hormones to their cell-surface receptors that activate PI-PLC by means of a guanine nucleotide binding protein. Activation of the enzyme leads to the hydrolysis of phosphatidylinositol 4,5-bisphosphate to two second messengers, 1,2-diacylglycerol and inositol 1,4,5-trisphosphate, the second of which ultimately mobilizes internal pools of calcium. There are at least five PI-PLC isoenzymes, whose differences in structure and function are unknown. We have focused on isoenzyme I, which we have recently purified and characterized from guinea pig uterus. We have now determined the sequence of a full length complementary DNA of this isoenzyme from the rat. Although the sequence has little similarity with the only other sequenced PI-PLC isoenzyme, it has a surprising degree of similarity to thioredoxins, protein co-factors in thiol-dependent redox reactions. 相似文献
34.
Genes required for ionizing radiation resistance in yeast. 总被引:1,自引:0,他引:1
C B Bennett L K Lewis G Karthikeyan K S Lobachev Y H Jin J F Sterling J R Snipe M A Resnick 《Nature genetics》2001,29(4):426-434
35.
A.贝涅特 《国外科技新书评介》2007,(2):8-8
本书是《剑桥力学专著》系列丛书之一。如今,对深海中声音跟踪漂浮物和卫星导航的地面移动物体观察系统的迫切需要,使人们对拉格朗日流体动力学重新产生兴趣。本书首先介绍拉格朗日框架下的经典解和新的精确解,接着讨论所得到的一般运动方程的可解性,最后论述湍流扩散和散射的统一考虑,并应用到海洋中的浮游生物片。 相似文献
36.
Eusociality, which occurs among mammals only in two species of African mole-rat, is characterized by division of labour between morphologically distinct 'castes'. In Damaraland mole-rats (Cryptomys damarensis), colony labour is divided between 'infrequent worker' and 'frequent worker' castes. Frequent workers are active year-round and together perform more than 95% of the total work of the colony, whereas infrequent workers typically perform less than 5% of the total work. Anecdotal evidence suggests that infrequent workers may act as dispersers, with dispersal being limited to comparatively rare periods when the soil is softened by moisture. Here we show that infrequent workers and queens increase their daily energy expenditure after rainfall whereas frequent workers do not. Infrequent workers are also fatter than frequent workers. We suggest that infrequent workers constitute a physiologically distinct dispersing caste, the members of which, instead of contributing to the work of the colony and helping the queen to reproduce, build up their own body reserves in preparation for dispersal and reproduction when environmental conditions are suitable. 相似文献
37.
Labelled free choline injected into the peritoneum failed to enter the brain but preferentially entered the liver. Subsequently labelled phospholipid was found in the plasma with a concurrent increase in the brain. This labelled plasma injected by cardiac puncture caused a rapid incorporation of the choline labelled phospholipid into the brain. 相似文献
38.
The insulin gene VNTR, type 2 diabetes and birth weight 总被引:12,自引:0,他引:12
Ong KK Phillips DI Fall C Poulton J Bennett ST Golding J Todd JA Dunger DB 《Nature genetics》1999,21(3):262-263
39.
Hereditary spherocytosis associated with deletion of human erythrocyte ankyrin gene on chromosome 8 总被引:27,自引:0,他引:27
S E Lux W T Tse J C Menninger K M John P Harris O Shalev R R Chilcote S L Marchesi P C Watkins V Bennett 《Nature》1990,345(6277):736-739
Hereditary spherocytosis (HS) is one of the most common hereditary haemolytic anaemias. HS red cells from both autosound dominant and recessive variants are spectrin-deficient, which correlates with the severity of the disease. Some patients with recessive HS have a mutation in the spectrin alpha-2 domain (S.L.M. et al., unpublished observations), and a few dominant HS patients have an unstable beta-spectrin that is easily oxidized, which damages the protein 4.1 binding site and weakens spectrin-actin interactions. In most patients, however, the cause of spectrin deficiency is unknown. The alpha- and beta-spectrin loci are on chromosomes 1 and 14 respectively. The only other genetic locus for HS is SPH2, on the short arm of chromosome 8 (8p11). This does not correspond to any of the known loci of genes for red cell membrane proteins including protein 4.1 (1p36.2-p34), the anion exchange protein (AE1, band 3; 17q21-qter), glycophorin C (2q14-q21), and beta-actin (7pter-q22). Human erythrocyte ankyrin, which links beta-spectrin to the anion exchange protein, has recently been cloned. We now show that the ankyrin gene maps to chromosome 8p11.2, and that one copy is missing from DNA of two unrelated children with severe HS and heterozygous deletions of chromosome 8 (del(8)(p11-p21.1)). Affected red cells are also ankyrin-deficient. The data suggest that defects or deficiency or ankyrin are responsible for HS at the SPH2 locus. 相似文献
40.
Modulation of spectrin-actin assembly by erythrocyte adducin 总被引:3,自引:0,他引:3
The spectrin-based membrane skeleton, an assembly of proteins tightly associated with the plasma membrane, determines the shape and mechanical properties of erythrocytes. Spectrin, the most abundant component of this assembly, is an elongated and flexible molecule that, with potentiation by protein 4.1, is cross-linked at its ends by short actin filaments to form a lattice beneath the membrane. These and other proteins stabilize the plasma membrane, organize integral membrane proteins and maintain specialized regions of the cell surface. A membrane-skeleton-associated calmodulin-binding protein of erythrocytes is a major substrate for Ca2+- and phospholipid-dependent protein kinase C (ref. 5), and thus is a target for Ca2+ by two regulatory pathways. Here we demonstrate that this protein, called adducin: (1) binds tightly in vitro to spectrin-actin complexes but with much less affinity either to spectrin or to actin alone; (2) promotes assembly of additional spectrin molecules onto actin filaments; and (3) is inhibited in its ability to induce the binding of additional spectrin molecules to actin by micromolar concentrations of calmodulin and Ca2+. Adducin may be involved in the action of Ca2+ on erythrocyte membrane skeleton and in the assembly of spectrin-actin complexes. 相似文献