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991.
992.
Mesolimbic dopamine-releasing neurons appear to be important in the brain reward system. One behavioural paradigm that supports this hypothesis is intracranial self-stimulation (ICS), during which animals repeatedly press a lever to stimulate their own dopamine-releasing neurons electrically. Here we study dopamine release from dopamine terminals in the nucleus accumbens core and shell in the brain by using rapid-responding voltammetric microsensors during electrical stimulation of dopamine cell bodies in the ventral tegmental area/substantia nigra brain regions. In rats in which stimulating electrode placement failed to elicit dopamine release in the nucleus accumbens, ICS behaviour was not learned. In contrast, ICS was acquired when stimulus trains evoked extracellular dopamine in either the core or the shell of the nucleus accumbens. In animals that could learn ICS, experimenter-delivered stimulation always elicited dopamine release. In contrast, extracellular dopamine was rarely observed during ICS itself. Thus, although activation of mesolimbic dopamine-releasing neurons seems to be a necessary condition for ICS, evoked dopamine release is actually diminished during ICS. Dopamine may therefore be a neural substrate for novelty or reward expectation rather than reward itself.  相似文献   
993.
Sigal LJ  Crotty S  Andino R  Rock KL 《Nature》1999,398(6722):77-80
Cytotoxic T lymphocytes (CTLs) are thought to detect viral infections by monitoring the surface of all cells for the presence of viral peptides bound to major histocompatibility complex (MHC) class I molecules. In most cells, peptides presented by MHC class I molecules are derived exclusively from proteins synthesized by the antigen-bearing cells. Macrophages and dendritic cells also have an alternative MHC class I pathway that can present peptides derived from extracellular antigens; however, the physiological role of this process is unclear. Here we show that virally infected non-haematopoietic cells are unable to stimulate primary CTL-mediated immunity directly. Instead, bone-marrow-derived cells are required as antigen-presenting cells (APCs) to initiate anti-viral CTL responses. In these APCs, the alternative (exogenous) MHC class I pathway is the obligatory mechanism for the initiation of CTL responses to viruses that infect only non-haematopoietic cells.  相似文献   
994.
Molecular basis of triclosan activity   总被引:19,自引:0,他引:19  
  相似文献   
995.
A capsaicin-receptor homologue with a high threshold for noxious heat   总被引:60,自引:0,他引:60  
Caterina MJ  Rosen TA  Tominaga M  Brake AJ  Julius D 《Nature》1999,398(6726):436-441
  相似文献   
996.
Gene mutations in invertebrates have been identified that extend life span and enhance resistance to environmental stresses such as ultraviolet light or reactive oxygen species. In mammals, the mechanisms that regulate stress response are poorly understood and no genes are known to increase individual life span. Here we report that targeted mutation of the mouse p66shc gene induces stress resistance and prolongs life span. p66shc is a splice variant of p52shc/p46shc (ref. 2), a cytoplasmic signal transducer involved in the transmission of mitogenic signals from activated receptors to Ras. We show that: (1) p66shc is serine phosphorylated upon treatment with hydrogen peroxide (H2O2) or irradiation with ultraviolet light; (2) ablation of p66shc enhances cellular resistance to apoptosis induced by H2O2 or ultraviolet light; (3) a serine-phosphorylation defective mutant of p66shc cannot restore the normal stress response in p66shc-/- cells; (4) the p53 and p21 stress response is impaired in p66shc-/- cells; (5) p66shc-/- mice have increased resistance to paraquat and a 30% increase in life span. We propose that p66shc is part of a signal transduction pathway that regulates stress apoptotic responses and life span in mammals.  相似文献   
997.
998.
本书是关于线性和非线性有限单元法的入门教材,是根据作者在过去12年里为美国新奥尔良大学的多个专业学生讲授这两门课程的基础上逐步编撰而成。本书不同于已有教材,有许多新颖的特点,如重视基础应用,力求最少涉及数学理论;内容涉及的专业范围宽,选用大量不同专业的问题进行引导,可供多种学科背景的学生学习;在讲述理论的同时将相关软件的使用贯穿全书。  相似文献   
999.
本书的第一、二、三版分别于1993、1999和2005年出版。书中全面提供了过去20年中在模式识别与计算机视觉领域中的进展和成就,作者都是这个领域的第一流专家,其中的两位Thomas Huang和Jake Aggarwal是权威的K.S.Fu奖金获得者,该项奖金是由国际模式识别协会(IAPR)授予。  相似文献   
1000.
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