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31.
Evidence for contractile protein translocation in macrophage spreading, phagocytosis, and phagolysosome formation 总被引:5,自引:4,他引:1 下载免费PDF全文
Macrophage pseudopodia that surround objects during phagocytosis contain a meshwork of actin filaments and exclude organelles. Between these pseudopodia at the base of developing phagosomes, the organelle exclusion ceases, and lysosomes enter the cell periphery to fuse with the phagosomes. Macrophages also extend hyaline pseudopodia on the surface of nylon wool fibers and secrete lysosomal enzymes into the extracellular medium instead of into phagosomes. To analyze biochemically these concurrent alterations in cytoplasmic architecture, we allowed rabbit lung macrophages to spread on nylon wool fibers and then subjected the adherent cells to shear. This procedure caused the selective release of β-glucoronidase into the extracellular medium and yielded two fractions, cell bodies and isolated pseudopod blebs resembling podosomes, which are plasma-lemma-bounded sacs of cortical cytoplasm. Cytoplasmic extracts of the cell bodies eluted from nylon fibers contained two-thirds less actin-binding protein and myosin, and approximately 20 percent less actin and two-thirds of the other two proteins were accounted for in podosomes. The alterations in protein composition correlated with assays of myosin-associated EDTA-activated adenosine triphosphatase activity, and with a diminution in the capacity of extracts of nylon wool fiber-treated cell bodies to gel, a property dependent on the interaction between actin-binding protein and F-actin. However, the capacity of the remaining actin in cell bodies to polymerize did not change. We propose that actin-binding protein and myosin are concentrated in the cell cortex and particularly in pseudopodia where prominent gelation and syneresis of actin occur. Actin in the regions from which actin-binding protein and myosin are displaced disaggregates without depolymerizing, permitting lysosomes to gain access to the plasmalemma. Translocation of contractile proteins could therefore account for the concomitant differences in organelle exclusion that characterize phagocytosis. 相似文献
32.
Expression and activity of the nucleotide-binding domains of the human ABCA1 transporter 总被引:1,自引:0,他引:1
Roosbeek S Caster H Liu QZ Berne PF Duverger N Christiaens B Vandekerckhove J Peelman F Labeur C Rosseneu M 《Protein expression and purification》2004,35(1):102-110
The aim of this study was the expression and production in Escherichia coli of the nucleotide-binding domains (NBDs) of the human ABCA1 transporter, in a soluble, non-denatured form. To increase the protein solubility, and avoid expression in E. coli inclusion bodies, we extended the length of the expressed NBD domains, to include proximal domains. The corresponding cDNA constructs were used to express the N-terminal His-tagged WT and mutant proteins, which were purified by Ni(2+)-affinity chromatography. Optimal expression of soluble proteins was obtained for constructs including the NBD, the downstream 80-residue domain, and about 20 upstream residues. The size homogeneity of WT and mutant NBDs was determined by Dynamic Light Scattering, and ATP-binding constants and ATPase activities were measured. The NBD1 and NBD2 domains bound ATP with comparable affinity. The ATPase activity of WT His-NBD1 was about three times higher than that of NBD2 and amounted to 5913 compared to 1979 nmol Pi/micromol NBD/min for WT His-NBD2. All engineered mutants had comparable ATPase activity to the corresponding WT protein. The optimisation of the length of the expressed proteins, based upon the boundary prediction of NBDs and neighbour domains, enables the expression and purification of soluble ABCA1 NBDs, with high ATPase activity. This approach should prove useful for the study of the structural and functional properties of the NBDs and other domains of the ABC transporters. 相似文献
33.
Ruis MA de Groot J te Brake JH Dinand Ekkel E van de Burgwal JA Erkens JH Engel B Buist WG Blokhuis HJ Koolhaas JM 《Applied animal behaviour science》2001,70(3):201-225
Endocrine, behavioural and immunologic processes, together with body growth, were evaluated in gilts that were defeated at 10 weeks of age in resident-intruder tests. Immediately after defeat, gilts were either separated from or reunited with a familiar conspecific (litter-mate; always a barrow). Gilts were assigned to one of four treatments: (a) DI: defeat, followed by isolation (separation from original litter-mate; n=8); (b) I: no defeat, isolation (control group; n=9); (c) DP; defeat, followed by pair-housing (reunion with original litter-mate; n=8); and (d) P: no defeat, pair-housing (control group; n=8). The following general conclusions were derived: (1) social defeat caused pronounced short-term elevations in hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal medullary activities, and of prolactin levels. Moreover, as soon as 1h after defeat, percentages of blood lymphocytes and neutrophilic granulocytes were, respectively, decreased and increased; (2) social defeat had some long-lasting influence on behaviour and physiology, but isolation predominantly determined responses in the longer term. Defeat, as well as isolation, resulted in increased cardiovascular activities compared to P controls, as observed in a novel object test (NOT: +7 days) and an aversion test (AVT: +14 days). Moreover, defeated as well as isolated gilts did not habituate to a repeated novel environment test (NET: -7, +2 and +7 days) in terms of frequencies of vocalising, whereas P controls did. Isolation, through the separation from any other pig, was responsible for the other observed long-term characteristics, which developed progressively. Isolated gilts showed high mobilities and high cortisol responses in the repeated NET (+7 days), not being habituated. This contrasted the reactions of pair-housed gilts, which were much reduced. In addition to their high cardiovascular activities in the NOT and the AVT, isolated gilts also displayed higher heart rates in the repeated NET and during human presence following the NOT, compared to pair-housed gilts. Finally, isolated gilts were more inhibited to approach a novel object (in the NOT) than pair-housed pigs; and (3) stress responses of defeated gilts were modulated by the subsequent social environment. Stimulation of the HPA-axis (plasma- and salivary cortisol) was prolonged in those defeated gilts which were isolated (observed in the first hour). Changes in leucocyte subsets were still observed after 3 days in DI, but were 'normalised' within 1 day in DP gilts. Two days after defeat, habituation to the repeated NET in terms of mobility and salivary cortisol responses occurred in control and DP gilts, but not in DI gilts. We argue that these effects of the social environment shortly after defeat were related to a stress-reducing effect of a stable social relationship, i.e. social support. 相似文献
34.
Isolation of a thymus hormone, LSH 总被引:2,自引:0,他引:2
35.
Background
Camouflage patterns that hinder detection and/or recognition by antagonists are widely studied in both human and animal contexts. Patterns of contrasting stripes that purportedly degrade an observer's ability to judge the speed and direction of moving prey ('motion dazzle') are, however, rarely investigated. This is despite motion dazzle having been fundamental to the appearance of warships in both world wars and often postulated as the selective agent leading to repeated patterns on many animals (such as zebra and many fish, snake, and invertebrate species). Such patterns often appear conspicuous, suggesting that protection while moving by motion dazzle might impair camouflage when stationary. However, the relationship between motion dazzle and camouflage is unclear because disruptive camouflage relies on high-contrast markings. In this study, we used a computer game with human subjects detecting and capturing either moving or stationary targets with different patterns, in order to provide the first empirical exploration of the interaction of these two protective coloration mechanisms.Results
Moving targets with stripes were caught significantly less often and missed more often than targets with camouflage patterns. However, when stationary, targets with camouflage markings were captured less often and caused more false detections than those with striped patterns, which were readily detected.Conclusions
Our study provides the clearest evidence to date that some patterns inhibit the capture of moving targets, but that camouflage and motion dazzle are not complementary strategies. Therefore, the specific coloration that evolves in animals will depend on how the life history and ontogeny of each species influence the trade-off between the costs and benefits of motion dazzle and camouflage. 相似文献36.
37.
The amyloid precursor protein (APP) is a ubiquitously expressed single-pass transmembrane protein that undergoes proteolytic processing by secretases to generate the pathogenic amyloid-β peptide, the major component in Alzheimer plaques. The traffic of APP through the cell determines its exposure to secretases and consequently the cleavages that generate the pathogenic or nonpathogenic peptide fragments. Despite the likely importance of APP traffic to Alzheimer disease, we still lack clear models for the routing and regulation of APP in cells. Like the traffic of most transmembrane proteins, the binding of adaptors to its cytoplasmic tail, which is 47 residues long and contains at least four distinct sorting motifs, regulates that of APP. We tested each of these for effects on the traffic of APP from the Golgi by mutating key residues within them and examining adaptor recruitment at the Golgi and traffic to post-Golgi site(s). We demonstrate strict specificity for recruitment of the Mint3 adaptor by APP at the Golgi, a critical role for Tyr-682 (within the YENPTY motif) in Mint3 recruitment and export of APP from the Golgi, and we identify LAMP1+ structures as the proximal destination of APP after leaving the Golgi. Together, these data provide a detailed view of the first sorting step in its route to the cell surface and processing by secretases and further highlight the critical role played by Mint3. 相似文献
38.
Ramajayam Govindan Venkatachalam Sivabalan Shazia Fathima JH Umaphathy Vidhya Rekha Senthilkumar Kalimuthu Selvaraj Jayaraman Kirubhanand Chandrasekaran 《Bioinformation》2020,16(11):937
The MUC1 oncoprotein is known to be linked with different types of cancer. Therefore, it is of interest to document the molecular docking analysis of compounds from Justica adhatoda L with the MUC1 oncoprotein. We report the structure based molecular binding features compounds such as amrinone, ethambutol, pyrazinamide and vasicoline the MUC1 oncoprotein for further consideration in drug discovery. 相似文献
39.
Erik JM Toonen Pilar Barrera Jaap Fransen Arjan PM de Brouwer Agnes M Eijsbouts Pierre Miossec Hubert Marotte Hans Scheffer Piet LCM van Riel Barbara Franke Marieke JH Coenen 《Arthritis research & therapy》2012,14(6):R264
Introduction
The goal of this study is to investigate whether the -308G > A promoter polymorphism in the tumor necrosis factor alpha (TNFA) gene is associated with disease severity and radiologic joint damage in a large cohort of patients with rheumatoid arthritis (RA).Methods
A long-term observational early RA inception cohort (n = 208) with detailed information about disease activity and radiologic damage after 3, 6 and 9 years of disease was genotyped for the TNFA -308G > A promoter polymorphism (rs1800629). A longitudinal regression analysis was performed to assess the effect of genotype on RA disease severity and joint damage. Subsequently, a meta-analysis, including all publically available data, was performed to further test the association between joint erosions and the TNFA polymorphism. To learn more about the mechanism behind the effect of the polymorphism, RNA isolated from peripheral blood from RA patients (n = 66) was used for TNFA gene expression analysis by quantitative PCR.Results
Longitudinal regression analysis with correction for gender and disease activity showed a significant difference in total joint damage between GG and GA+AA genotype groups (P = 0.002), which was stable over time. The meta-analysis, which included 2,053 patients, confirmed an association of the genetic variant with the development of erosions (odds ratio 0.78, 95% CI 0.62, 0.98). No significant differences in TNFA gene expression were observed for the different genotypes, confirming earlier findings in healthy individuals.Conclusions
Our data confirm that the TNFA -308G > A promoter polymorphism is associated with joint damage in patients with RA. This is not mediated by differences in TNFA gene expression between genotypes. 相似文献40.
Frank JH Gijsen Francesco Migliavacca Silvia Schievano Laura Socci Lorenza Petrini Attila Thury Jolanda J Wentzel Anton FW van der Steen Patrick WS Serruys Gabriele Dubini 《Biomedical engineering online》2008,7(1):23