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141.
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143.
Purification and cloning of amyloid precursor protein beta-secretase from human brain 总被引:40,自引:0,他引:40
Sinha S Anderson JP Barbour R Basi GS Caccavello R Davis D Doan M Dovey HF Frigon N Hong J Jacobson-Croak K Jewett N Keim P Knops J Lieberburg I Power M Tan H Tatsuno G Tung J Schenk D Seubert P Suomensaari SM Wang S Walker D Zhao J McConlogue L John V 《Nature》1999,402(6761):537-540
Proteolytic processing of the amyloid precursor protein (APP) generates amyloid beta (Abeta) peptide, which is thought to be causal for the pathology and subsequent cognitive decline in Alzheimer's disease. Cleavage by beta-secretase at the amino terminus of the Abeta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated carboxy-terminal fragment. Cleavage of the C-terminal fragment by gamma-secretase(s) leads to the formation of Abeta. The pathogenic mutation K670M671-->N670L671 at the beta-secretase cleavage site in APP, which was discovered in a Swedish family with familial Alzheimer's disease, leads to increased beta-secretase cleavage of the mutant substrate. Here we describe a membrane-bound enzyme activity that cleaves full-length APP at the beta-secretase cleavage site, and find it to be the predominant beta-cleavage activity in human brain. We have purified this enzyme activity to homogeneity from human brain using a new substrate analogue inhibitor of the enzyme activity, and show that the purified enzyme has all the properties predicted for beta-secretase. Cloning and expression of the enzyme reveals that human brain beta-secretase is a new membrane-bound aspartic proteinase. 相似文献
144.
Nanostructured materials have drawn considerable attention because they are promising candidates for nextgeneration electronic and photonic devices with low power consumption[1-5]. A number of methods, such as laser ablation[6], template-induced growth[7], arc discharge [8], vapor transport [9], and molecular-beam epitaxy[10] have been developed to synthesize Si, Ge, MgO,SnO2, GaN, and Ga2O3 nanowires or nanorods[11-15]. 相似文献
145.
146.
卫星低频电磁辐射在轨探测研究 总被引:2,自引:0,他引:2
利用地球空间探测双星计划探测一号卫星上的磁场波动分析仪的原始数据, 分析了探测一号卫星在轨电磁辐射的特性. 结果显示卫星的电磁辐射主要集中在30 Hz以下. 在30 Hz以上, 卫星的电磁辐射最多延伸到 190 Hz左右, 而且强度明显减弱. 在 190 Hz以下的卫星电磁辐射具有与卫星姿态相关的长周期变化. 在 190~830 Hz的范围的电磁辐射有不明显的长周期变化特征. 830~3990 Hz范围的电磁辐射没有长周期变化特征. 卫星电磁辐射的长周期变化是由卫星姿态变化造成的. 卫星姿态变化引起卫星太阳方位角变化. 卫星太阳方位角越大, 卫星电磁辐射越大. 卫星太阳方位角从90.6增加到93.6, 低于10 Hz以下的电磁辐射约增大为原来的9倍, 10~190 Hz范围的电磁辐射大约增加到原来的1.6倍. 卫星在<10和10~190 Hz范围内的电磁辐射强度与卫星太阳方位角的相关系数分别达到0.90和0.91. 卫星在光照情况下的电磁辐射要比卫星在阴影情况下大. 卫星太阳能帆板电流产生的电磁辐射是卫星电磁辐射主要来源, 约占整个卫星电磁辐射的87%(低频段<150 Hz)和94%(高频段>150 Hz). 这些中国首次对卫星电磁辐射的在轨探测结果对于我国未来相关科学和应用卫星的设计方案的优化具有重要的参考价值. 相似文献
147.
Cloning of a representative genomic library of the human X chromosome after sorting by flow cytometry 总被引:54,自引:0,他引:54
A library of 50,000 recombinants representative of the human X chromosome has been constructed. Human X chromosomes were physically separated using a fluorescence-activated cell sorter. The DNA was purified from the chromosomes, digested to completion with the restriction enzyme EcoRI and cloned into the phage lambda gtWES.lambda B. The X-derived nature of the recombinants was confirmed by hybridization to rodent/human cell line DNA containing only the human X chromosome. Such libraries will be particularly useful for the investigation of genetic diseases such as Duchenne muscular dystrophy, where the basic defect has not been elucidated, and of neoplasia, where several specific chromosomal anomalies, particularly for the leukaemias, have been identified. 相似文献
148.
Anthropogenic ocean acidification over the twenty-first century and its impact on calcifying organisms 总被引:15,自引:0,他引:15
Orr JC Fabry VJ Aumont O Bopp L Doney SC Feely RA Gnanadesikan A Gruber N Ishida A Joos F Key RM Lindsay K Maier-Reimer E Matear R Monfray P Mouchet A Najjar RG Plattner GK Rodgers KB Sabine CL Sarmiento JL Schlitzer R Slater RD Totterdell IJ Weirig MF Yamanaka Y Yool A 《Nature》2005,437(7059):681-686
Today's surface ocean is saturated with respect to calcium carbonate, but increasing atmospheric carbon dioxide concentrations are reducing ocean pH and carbonate ion concentrations, and thus the level of calcium carbonate saturation. Experimental evidence suggests that if these trends continue, key marine organisms--such as corals and some plankton--will have difficulty maintaining their external calcium carbonate skeletons. Here we use 13 models of the ocean-carbon cycle to assess calcium carbonate saturation under the IS92a 'business-as-usual' scenario for future emissions of anthropogenic carbon dioxide. In our projections, Southern Ocean surface waters will begin to become undersaturated with respect to aragonite, a metastable form of calcium carbonate, by the year 2050. By 2100, this undersaturation could extend throughout the entire Southern Ocean and into the subarctic Pacific Ocean. When live pteropods were exposed to our predicted level of undersaturation during a two-day shipboard experiment, their aragonite shells showed notable dissolution. Our findings indicate that conditions detrimental to high-latitude ecosystems could develop within decades, not centuries as suggested previously. 相似文献
149.
本文扼要介绍了作者收集、整理目前已发现的所有药物及其作用靶点的相关信息,并整合现代分子生物、药物、化学等的最新进展,采用业界领先的Java的j2ee框架,建立一个综合的数据库系统的过程。同时在该综合数据库系统的基础上,嵌入药物分子和靶点的对接技术,使得我们的系统除用于一般的药物分子和靶点查询之外,还能实现基于分子反向对接的虚拟筛选和通过药物分子寻找其作用的潜在蛋白靶点。本数据库暂时只能本机访问,对外访问地址尚在建设中。 相似文献
150.
Soil fertility limits carbon sequestration by forest ecosystems in a CO2-enriched atmosphere 总被引:15,自引:0,他引:15
Oren R Ellsworth DS Johnsen KH Phillips N Ewers BE Maier C Schäfer KV McCarthy H Hendrey G McNulty SG Katul GG 《Nature》2001,411(6836):469-472
Northern mid-latitude forests are a large terrestrial carbon sink. Ignoring nutrient limitations, large increases in carbon sequestration from carbon dioxide (CO2) fertilization are expected in these forests. Yet, forests are usually relegated to sites of moderate to poor fertility, where tree growth is often limited by nutrient supply, in particular nitrogen. Here we present evidence that estimates of increases in carbon sequestration of forests, which is expected to partially compensate for increasing CO2 in the atmosphere, are unduly optimistic. In two forest experiments on maturing pines exposed to elevated atmospheric CO2, the CO2-induced biomass carbon increment without added nutrients was undetectable at a nutritionally poor site, and the stimulation at a nutritionally moderate site was transient, stabilizing at a marginal gain after three years. However, a large synergistic gain from higher CO2 and nutrients was detected with nutrients added. This gain was even larger at the poor site (threefold higher than the expected additive effect) than at the moderate site (twofold higher). Thus, fertility can restrain the response of wood carbon sequestration to increased atmospheric CO2. Assessment of future carbon sequestration should consider the limitations imposed by soil fertility, as well as interactions with nitrogen deposition. 相似文献