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61.
Designing CD4 immunoadhesins for AIDS therapy 总被引:66,自引:0,他引:66
D J Capon S M Chamow J Mordenti S A Marsters T Gregory H Mitsuya R A Byrn C Lucas F M Wurm J E Groopman 《Nature》1989,337(6207):525-531
A newly-constructed antibody-like molecule containing the gp120-binding domain of the receptor for human immunodeficiency virus blocks HIV-1 infection of T cells and monocytes. Its long plasma half-life, other antibody-like properties, and potential to block all HIV isolates, make it a good candidate for therapeutic use. 相似文献
62.
Caro Lucas 《系统科学与复杂性》1993,(4)
The purpose of this paper is to present a unified theory of several differentneural networks that have been proposed for solving various computation, pattern recog-nition, imaging, optimization, and other problems. The functioning of these networks ischaracterized by Lyapunov energy functions. The relationship between the deterministicand stochastic neural networks is examined. The simulated annealing methods for findingthe global optimum of an objective function as well as their generalization by injectingnoise into deterministic neural networks are discussed. A statistical interpretation of thedynamic evolution of the different neural networks is presented. The problem of trainingdifferent neural networks is investigated in this general framework. It is shown how thisapproach can be used not only for analyzing various neural networks, but also for the choiceof the proper neural network for solving any given problem and the design of a trainingalgorithm for the particular neural network. 相似文献
63.
64.
P. D. Lucas 《Cellular and molecular life sciences : CMLS》1987,43(8):894-895
Summary Tibial growth and blood flow were both found to be markedly reduced in anaesthetised streptozotocin-diabetic rats compared to controls. Insulin treatment restored tibial growth to approximately control values and increased tibial blood flow to above control values. The observations are likely to be related to reduced bone turnover in uncontrolled diabetes.25 November 1986 相似文献
65.
66.
The T lymphocyte surface protein CD4 is an integral membrane glycoprotein noncovalently associated with the tyrosine protein kinase p56lck. In normal T cells, surface association of CD4 molecules with other CD4 molecules or other T-cell surface proteins, such as the T-cell antigen receptor, stimulates the activity of the p56lck tyrosine kinase, resulting in the phosphorylation of various cellular proteins at tyrosine residues. Thus, the signal transduction in T cells generated through the surface engagement of CD4 is similar to that observed for the class of growth factor receptors possessing endogenous tyrosine kinase activity. As CD4 is also the cellular receptor for the human immunodeficiency virus (HIV), binding of the virus or gp120 (the virus surface protein responsible for specific CD4+ T-cell association) could mimic the types of immunological interactions that have previously been found to stimulate p56lck and trigger T-cell activation pathways. We have evaluated this possibility and report here that binding of HIV-1 or the virus glycoprotein gp120 to CD4+ human T cells fails to elicit detectable p56lck-dependent tyrosine kinase activation and signalling, alterations in the composition of cellular phosphotyrosine-containing proteins, or changes in intracellular Ca2+ concentration. 相似文献
67.
Prevention of HIV-1 IIIB infection in chimpanzees by CD4 immunoadhesin 总被引:11,自引:0,他引:11
R H Ward D J Capon C M Jett K K Murthy J Mordenti C Lucas S W Frie A M Prince J D Green J W Eichberg 《Nature》1991,352(6334):434-436
The first step in infection by the human immunodeficiency virus (HIV) is the specific binding of gp120, the envelope glycoprotein of HIV, to its cellular receptor, CD4. To inhibit this interaction, soluble CD4 analogues that compete for gp120 binding and block HIV infection in vitro have been developed. To determine whether these analogues can protect an uninfected individual from challenge with HIV, we used the chimpanzee model system of cell-free HIV infection. Chimpanzees are readily infected with the IIIB strain of HIV-1, becoming viraemic within about 4-6 weeks of challenge, although they do not develop the profound CD4+ T-cell depletion and immunodeficiency characteristic of HIV infection in humans. CD4 immunoadhesin (CD4-IgG), a chimaeric molecule consisting of the N-terminal two immunoglobulin-like regions of CD4 joined to the Fc region of human IgG1, was selected as the CD4 analogue for testing because it has a longer half-life than CD4, contributed by the IgG Fc portion of the molecule. In humans, this difference results in a 25-fold increased concentration of CD4-IgG in the blood compared with recombinant CD4. Here we report that pretreatment with CD4-IgG can prevent the infection of chimpanzees with HIV-1. The need for a preventative agent is particularly acute in perinatal HIV transmission. As recombinant CD4-IgG, like the parent IgG molecule, efficiently crosses the primate placenta, it may be possible to set up an immune state in a fetus before HIV transfer occurs, thus preventing infection. 相似文献
68.
de Lucas M Davière JM Rodríguez-Falcón M Pontin M Iglesias-Pedraz JM Lorrain S Fankhauser C Blázquez MA Titarenko E Prat S 《Nature》2008,451(7177):480-484
69.
Wain LV Verwoert GC O'Reilly PF Shi G Johnson T Johnson AD Bochud M Rice KM Henneman P Smith AV Ehret GB Amin N Larson MG Mooser V Hadley D Dörr M Bis JC Aspelund T Esko T Janssens AC Zhao JH Heath S Laan M Fu J Pistis G Luan J Arora P Lucas G Pirastu N Pichler I Jackson AU Webster RJ Zhang F Peden JF Schmidt H Tanaka T Campbell H Igl W Milaneschi Y Hottenga JJ Vitart V Chasman DI Trompet S Bragg-Gresham JL Alizadeh BZ Chambers JC Guo X Lehtimäki T Kühnel B Lopez LM Polašek O Boban M Nelson CP 《Nature genetics》2011,43(10):1005-1011
Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP. 相似文献
70.
Bencherif M Lippiello PM Lucas R Marrero MB 《Cellular and molecular life sciences : CMLS》2011,68(6):931-949
In recent years the etiopathology of a number of debilitating diseases such as type 2 diabetes, arthritis, atherosclerosis,
psoriasis, asthma, cystic fibrosis, sepsis, and ulcerative colitis has increasingly been linked to runaway cytokine-mediated
inflammation. Cytokine-based therapeutic agents play a major role in the treatment of these diseases. However, the temporospatial
changes in various cytokines are still poorly understood and attempts to date have focused on the inhibition of specific cytokines
such as TNF-α. As an alternative approach, a number of preclinical studies have confirmed the therapeutic potential of targeting
alpha7 nicotinic acetylcholine receptor-mediated anti-inflammatory effects through modulation of proinflammatory cytokines.
This “cholinergic anti-inflammatory pathway” modulates the immune system through cholinergic mechanisms that act on alpha7
receptors expressed on macrophages and immune cells. If the preclinical findings translate into human efficacy this approach
could potentially provide new therapies for treating a broad array of intractable diseases and conditions with inflammatory
components. 相似文献