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排序方式: 共有1034条查询结果,搜索用时 15 毫秒
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Rogaeva E Meng Y Lee JH Gu Y Kawarai T Zou F Katayama T Baldwin CT Cheng R Hasegawa H Chen F Shibata N Lunetta KL Pardossi-Piquard R Bohm C Wakutani Y Cupples LA Cuenco KT Green RC Pinessi L Rainero I Sorbi S Bruni A Duara R Friedland RP Inzelberg R Hampe W Bujo H Song YQ Andersen OM Willnow TE Graff-Radford N Petersen RC Dickson D Der SD Fraser PE Schmitt-Ulms G Younkin S Mayeux R Farrer LA St George-Hyslop P 《Nature genetics》2007,39(2):168-177
The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into Abeta-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease. 相似文献
3.
K K Leong K M Yu W B Lee 《厦门大学学报(自然科学版)》2002,(Z1)
Product data management (PDM) has been accepted as an important tool for the manufacturing industries. In recent years, more and mor e researches have been conducted in the development of PDM. Their research area s include system design, integration of object-oriented technology, data distri bution, collaborative and distributed manufacturing working environment, secur ity, and web-based integration. However, there are limitations on their rese arches. In particular, they cannot cater for PDM in dis... 相似文献
4.
Many molecules can rotate freely around single bonds and thereby interconvert between different conformations, such as gauche and anti 1,2-disubstituted ethane, a classic example of conformational isomerism. Even though rotation occurs rapidly at room temperature, the product selectivity seen in some reactions has been explained by conformation-dependent reaction mechanisms: if reactant molecules differing only in their conformation are located at different positions on the reaction path, they may undergo different reactions. But a direct verification of this effect is difficult, because the energy barrier separating conformational isomers is so low that under ambient conditions reactants with more than one conformation will be present. But by using temperatures low enough to suppress the interconversion between different conformations, gauche-1-iodopropane ions and anti-1-iodopropane ions have been selectively generated. Here we show that the kinetic energy released during the photodissociation of 1-iodopropane ions depends strongly on the conformation of the ions. Thermodynamic arguments and ab initio calculations indicate that this difference in kinetic energy release results from differences in the reaction mechanism, with gauche-1-iodopropane ions forming 2-propyl ions and anti-1-iodopropane ions forming protonated cyclopropane ions. These findings suggest that the well-known concept of conformation selection forms the basis of a simple scheme for reaction control, thus providing in some cases an attractive alternative for more involved schemes that utilize the phase and pulse shape of laser beams to control chemical reactions. 相似文献
5.
LOGISTICS SCHEDULING: ANALYSIS OFTWO-STAGE PROBLEMS 总被引:4,自引:0,他引:4
This paper studies the coordination effects between stages for scheduling problems where decision-making is a two-stage process. Two stages are considered as one system. The system can be a supply chain that links two stages, one stage representing a manufacturer; and the other, a distributor It also can represent a single manufacturer, while each stage represents a different department responsible for a part of operations. A problem that jointly considers both stages in order to achieve ideal overall system performance is defined as a system problem. In practice, at times, it might not be feasible for the two stages to make coordinated decisions due to (i) the lack of channels that allow decision makers at the two stages to cooperate, and/or (ii) the optimal solution to the system problem is too difficult (or costly) to achieve.Two practical approaches are applied to solve a variant of two-stage logistic scheduling problems. The Forward Approach is defined as a solution procedure by which the first sta 相似文献
6.
McCarroll SA Hadnott TN Perry GH Sabeti PC Zody MC Barrett JC Dallaire S Gabriel SB Lee C Daly MJ Altshuler DM;International HapMap Consortium 《Nature genetics》2006,38(1):86-92
The locations and properties of common deletion variants in the human genome are largely unknown. We describe a systematic method for using dense SNP genotype data to discover deletions and its application to data from the International HapMap Consortium to characterize and catalogue segregating deletion variants across the human genome. We identified 541 deletion variants (94% novel) ranging from 1 kb to 745 kb in size; 278 of these variants were observed in multiple, unrelated individuals, 120 in the homozygous state. The coding exons of ten expressed genes were found to be commonly deleted, including multiple genes with roles in sex steroid metabolism, olfaction and drug response. These common deletion polymorphisms typically represent ancestral mutations that are in linkage disequilibrium with nearby SNPs, meaning that their association to disease can often be evaluated in the course of SNP-based whole-genome association studies. 相似文献
7.
Existing home devices in home network provides only independent services limited on a homogeneous protocol and/or do not fully support an intelligent service provided by cooperating among heterogeneous protocol devices. This paper proposes an intelligent and integrated service binding architecture which allow the users to figure out the status of devices and to cooperate among home network devices regardless of supported protocols or operational characteristics. 相似文献
8.
李椿浩 《西安联合大学学报》2007,10(1):54-56
公元307年,王弥反晋起义失败后,决心依附匈奴汉国。他和刘渊“深有分契”,尽量利用汉国的名义,其势力逐渐达到“东王青州”的程度。他成为匈奴汉国地方武装势力后,始终以半独立的状态存在。将以王弥为例,寻找汉国地方武装势力的生存过程,并分析其地方统治模式是一件颇为有意义的工作。 相似文献
9.
Gout AM;ADPKD Gene Variant Consortium Ravine D Harris PC Rossetti S Peters D Breuning M Henske EP Koizumi A Inoue S Shimizu Y Thongnoppakhun W Yenchitsomanus PT Deltas C Sandford R Torra R Turco AE Jeffery S Fontes M Somlo S Furu LM Smulders YM Mercier B Ferec C Burtey S Pei Y Kalaydjieva L Bogdanova N McCluskey M Geon LJ Wouters CH Reiterova J Stekrová J San Millan JL Aguiari G Del Senno L 《Nature genetics》2007,39(4):427-428
10.
Wai-Hung Ng S F Lee 《厦门大学学报(自然科学版)》2002,(Z1)
With a unique corporate culture based on ancient Ch in ese wisdom being implemented at workplace for more than 10 years, we have been e ncountering various issue of managing conflicts, in particular at organization r estructure period, although we perceive that conflict does not necessarily have dysfunctional effect on our group performance. However, conflicts between and am ong various levels of the organization hierarchy are inevitably creating certain impact on our organization cohesiveness, performa... 相似文献