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41.
HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites 总被引:54,自引:0,他引:54
Kwong PD Doyle ML Casper DJ Cicala C Leavitt SA Majeed S Steenbeke TD Venturi M Chaiken I Fung M Katinger H Parren PW Robinson J Van Ryk D Wang L Burton DR Freire E Wyatt R Sodroski J Hendrickson WA Arthos J 《Nature》2002,420(6916):678-682
The ability of human immunodeficiency virus (HIV-1) to persist and cause AIDS is dependent on its avoidance of antibody-mediated neutralization. The virus elicits abundant, envelope-directed antibodies that have little neutralization capacity. This lack of neutralization is paradoxical, given the functional conservation and exposure of receptor-binding sites on the gp120 envelope glycoprotein, which are larger than the typical antibody footprint and should therefore be accessible for antibody binding. Because gp120-receptor interactions involve conformational reorganization, we measured the entropies of binding for 20 gp120-reactive antibodies. Here we show that recognition by receptor-binding-site antibodies induces conformational change. Correlation with neutralization potency and analysis of receptor-antibody thermodynamic cycles suggested a receptor-binding-site 'conformational masking' mechanism of neutralization escape. To understand how such an escape mechanism would be compatible with virus-receptor interactions, we tested a soluble dodecameric receptor molecule and found that it neutralized primary HIV-1 isolates with great potency, showing that simultaneous binding of viral envelope glycoproteins by multiple receptors creates sufficient avidity to compensate for such masking. Because this solution is available for cell-surface receptors but not for most antibodies, conformational masking enables HIV-1 to maintain receptor binding and simultaneously to resist neutralization. 相似文献
42.
Kinins in cerebrospinal fluid: reduced concentration in spontaneously hypertensive rats 总被引:1,自引:0,他引:1
Rat cerebrospinal fluid contains peptides which displace radiolabeled bradykinin from its specific antibodies. Two peptides which showed the same retention time as kallidin and bradykinin in a reverse phase high pressure liquid chromatography system were detected in cerebrospinal fluid of rats. The concentration of radioimmunologically detected kinins in the cerebrospinal fluid of spontaneously hypertensive rats of the Okamoto strain was lower than that of the Wistar Kyoto control rats. 相似文献
43.
WANG Hui MA ShuYing Hermann LUEHR ZHOU YunLiang DANG Ge 《科学通报(英文版)》2007,52(2):248-258
With geomagnetic measurements on board of CHAMP satellite, the characteristics of global large-scale field-aligned currents (FACs) in the topside ionosphere are investigated along with their responses to interplanetary conditions for the superstorm of November, 2003. It is found that (1) The storm-time FAC densities enhanced greatly in comparison with quiet period and the enhancements show hemispheric asymmetry of both summer-winter and sunlit-dark. (2) For the first time, it is revealed that the lati- tude-integrated FAC density is controlled mainly by solar wind dynamic pressure rather than iMF. (3) FACs expanded equatorward dramatically, with the lowest latitude being 45° MLat or more; on the dayside this expansion was controlled directly by IMF Bz, showing an interaction time scale of about 25 min in the solar wind-magnetosphere-ionosphere coupling system, and a nonlinear saturation of the equatorward expansion when IMF Bz 〈 -30 nT; while on the nightside, the expansion and recovery lagged about 3 h behind the IMF changes but nearly in phase with changes of SYM-H index. (4) During the storm main phase, the nightside FAC latitude coverage extended to 25° or wider, appearing multi-sheet current structure with more than 10 sheets. 相似文献
44.
Prion diseases are fatal neurodegenerative and infectious disorders of humans and animals, characterized by structural transition
of the host-encoded cellular prion protein (PrPc) into the aberrantly folded pathologic isoform PrPSc. RNA, DNA or peptide aptamers are classes of molecules which can be selected from complex combinatorial libraries for high
affinity and specific binding to prion proteins and which might therefore be useful in diagnosis and therapy of prion diseases.
Nucleic acid aptamers, which can be chemically synthesized, stabilized and immobilized, appear more suitable for diagnostic
purposes, allowing use of PrPSc as selection target. Peptide aptamers facilitate appropriate intracellular expression, targeting and re-routing without losing
their binding properties to PrP, a requirement for potential therapeutic gene transfer experiments in vivo. Elucidation of
structural properties of peptide aptamers might be used as basis for rational drug design, providing another attractive application
of peptide aptamers in the search for effective anti-prion strategies. 相似文献
45.
Shuai Chen Nan Qu Shouyun Cao Bauwe Hermann Shouyi Chen Wenzhong Tian Chengcai Chu 《科学通报(英文版)》2001,46(19):1635-1638
ThegdcsP promoter isolated from C3-C4 intermediate plantFlaveria anomala was fused to the β-glucuronidase (GUS) gene. The chimeric gene was inserted into the binary vector pBin19 and introduced
into the rice (Oryza sativa L.) cv. 8706 byAgrobacteriummediated gene transfer. GUS activity can be detected in leaf, leaf sheath, stem and root tissues via fluorometric GUS assay. However,
no GUS activity was found in mature endosperm. Histochemical localization revealed that GUS expression was exclusively restricted
to vascular tissues in transgenic plants. This promoter also showed spatial-temporal expression patterns that GUS expression
declined significantly with the maturity of plants. These expression patterns make thegdcsP promoter extremely valuable in the applied biotechnology that needs target gene expression restricted to vascular tissues. 相似文献
46.
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48.
Summary A colorimetric method for the determination of thyroxin has been worked out. Directions for practical use are given. 相似文献
49.
Florian Hochapfel Lucia Denk Gudrun Mendl Ulf Schulze Christine Maaßen Yulia Zaytseva Hermann Pavenstädt Thomas Weide Reinhard Rachel Ralph Witzgall Michael P. Krahn 《Cellular and molecular life sciences : CMLS》2017,74(24):4573-4586
Mammalian podocytes, the key determinants of the kidney’s filtration barrier, differentiate from columnar epithelial cells and several key determinants of apical–basal polarity in the conventional epithelia have been shown to regulate podocyte morphogenesis and function. However, little is known about the role of Crumbs, a conserved polarity regulator in many epithelia, for slit-diaphragm formation and podocyte function. In this study, we used Drosophila nephrocytes as model system for mammalian podocytes and identified a conserved function of Crumbs proteins for cellular morphogenesis, nephrocyte diaphragm assembly/maintenance, and endocytosis. Nephrocyte-specific knock-down of Crumbs results in disturbed nephrocyte diaphragm assembly/maintenance and decreased endocytosis, which can be rescued by Drosophila Crumbs as well as human Crumbs2 and Crumbs3, which were both expressed in human podocytes. In contrast to the extracellular domain, which facilitates nephrocyte diaphragm assembly/maintenance, the intracellular FERM-interaction motif of Crumbs is essential for regulating endocytosis. Moreover, Moesin, which binds to the FERM-binding domain of Crumbs, is essential for efficient endocytosis. Thus, we describe here a new mechanism of nephrocyte development and function, which is likely to be conserved in mammalian podocytes. 相似文献
50.
The genesis of the exon–intron patterns of eukaryotic genes persists as one of the most enigmatic questions in molecular genetics.
In particular, the origin and mechanisms responsible for creation of spliceosomal introns have remained controversial. Now
the issue appears to have taken a turn. The formation of novel introns in eukaryotes, including some vertebrate lineages,
is not as rare as commonly assumed. Moreover, introns appear to have been gained in parallel at closely spaced sites and even
repeatedly at the same position. Based on these discoveries, novel hypotheses of intron creation have been developed. The
new concepts posit that DNA repair processes are a major source of intron formation. Here, after summarizing the current views
of intron gain mechanisms, I review findings in support of the DNA repair hypothesis that provides a global mechanistic scenario
for intron creation. Some implications on our perception of the mosaic structure of eukaryotic genes are also discussed. 相似文献