首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   1407篇
  免费   79篇
  国内免费   5篇
耳鼻咽喉   17篇
儿科学   50篇
妇产科学   18篇
基础医学   123篇
口腔科学   42篇
临床医学   138篇
内科学   267篇
皮肤病学   11篇
神经病学   48篇
特种医学   334篇
外科学   136篇
综合类   29篇
预防医学   137篇
眼科学   18篇
药学   70篇
  1篇
中国医学   8篇
肿瘤学   44篇
  2021年   20篇
  2020年   9篇
  2018年   21篇
  2017年   9篇
  2016年   20篇
  2015年   22篇
  2014年   16篇
  2013年   50篇
  2012年   51篇
  2011年   55篇
  2010年   45篇
  2009年   44篇
  2008年   37篇
  2007年   39篇
  2006年   46篇
  2005年   34篇
  2004年   22篇
  2003年   43篇
  2002年   32篇
  2001年   29篇
  2000年   36篇
  1999年   34篇
  1998年   44篇
  1997年   37篇
  1996年   39篇
  1995年   48篇
  1994年   39篇
  1993年   37篇
  1992年   20篇
  1991年   7篇
  1990年   23篇
  1989年   46篇
  1988年   30篇
  1987年   30篇
  1986年   41篇
  1985年   32篇
  1984年   24篇
  1983年   18篇
  1982年   17篇
  1981年   25篇
  1980年   21篇
  1979年   13篇
  1978年   24篇
  1977年   20篇
  1976年   16篇
  1975年   17篇
  1972年   11篇
  1971年   8篇
  1967年   8篇
  1966年   10篇
排序方式: 共有1491条查询结果,搜索用时 15 毫秒
81.
The molecular mechanisms underlying polarized sorting of proteins in neurons are poorly understood. Here we report the identification of a 16 amino-acid, dileucine-containing motif that mediates dendritic targeting in a variety of neuronal cell types in slices of rat brain. This motif is present in the carboxy (C) termini of Shal-family K+ channels and is highly conserved from C. elegans to humans. It is necessary for dendritic targeting of potassium channel Kv4.2 and is sufficient to target the axonally localized channels Kv1.3 and Kv1.4 to the dendrites. It can also mediate dendritic targeting of a non-channel protein, CD8.  相似文献   
82.
83.
A team of researchers, including one behavioral scientist (S.M.N.) and three epidemiologists (L.Q., O.S. and S.N.) conducted community analyses to assess the social and cultural factors that affect the detection and reporting of disease cases in a surveillance system, using acute flaccid paralysis (AFP) surveillance in Niger as a case study. Over a 60-day period in the country, the research team reviewed written field reports and interviewed epidemiologists, nurses, community members and persons in governmental and non-governmental organizations. Overall, we found that the logistical difficulties of travel and communication, which are common in developing countries, constrain the conventional surveillance system that relies on epidemiologists visiting sites to discover and investigate cases, particularly in rural areas. Other challenges include: community members' lack of knowledge about the possible link between a case of paralysis and a dangerous, communicable disease; lack of access to health care, including the low number of clinics and health care workers; cultural beliefs that favor seeking a local healer before consulting a nurse or physician; and health workers' lack of training in AFP surveillance. The quality of surveillance in developing countries can improve if a community-based approach is adopted. Such a system has been used successfully in Niger during smallpox-eradication and guinea worm-control campaigns. In a community-based system, community members receive basic education or more extensive training to motivate and enable them to notify health care staff about possible cases of disease in a timely fashion. Local organizations, local projects and local leaders must be included to ensure the success of such a program. In Niger we found sufficient quantities of this type of social capital, along with enough local experience of past health campaigns, to suggest that a community-based approach can improve the level of comprehensiveness and sensitivity of surveillance.  相似文献   
84.
(1) Atropine, a classical muscarinic antagonist, has been reported previously to inhibit neuronal nicotinic acetylcholine receptors (nAChRs). In the present study, the action of atropine has been examined on alpha3beta4 receptors expressed heterologously in Xenopus oocytes and native nAChRs in medial habenula neurons. (2) At concentrations of atropine often used to inhibit muscarinic receptors (1 micro M), responses induced by near-maximal nicotine concentrations (100 micro M) at negative holding potentials (-65 mV) are inhibited (14-30%) in a reversible manner in both alpha4 and alpha3 subunit-containing heteromeric nAChRs. Half-maximal effective concentrations (IC(50) values) for atropine inhibition are similar for the four classes of heteromeric receptors studied (4-13 micro M). (3) For alpha3beta4 nAChRs in oocytes, inhibition by atropine (10 micro M) is not overcome at higher concentrations of agonist, and is increased with membrane hyperpolarization. These results are consistent with non-competitive antagonism--possibly ion channel block. (4) At low concentrations of both nicotine (10 micro M) and atropine (<10 micro M), potentiation ( approximately 25%) of alpha3beta4 nAChR responses in oocytes is observed. The relative balance between potentiation and inhibition is dependent upon membrane potential. (5) In rat medial habenula (MHb) neurons, atropine (0.3-3.0 micro M) inhibited nicotine-induced responses in both a concentration and membrane potential-dependent manner (at -40 mV, IC(50)=4 micro M), similar to the effects on alpha3beta4-nAChRs in oocytes. However, unlike heterologously expressed receptors, potentiation was barely detectable at depolarized membrane potentials using low concentrations of nicotine (3-10 micro M). Conversely, the weak agonist, choline (1-3 mM) was observed to augment responses of MHb nAChRs.  相似文献   
85.
Neurotransmitter transporters couple the transport of transmitter against its concentration gradient to the electrochemical potential of associated ions which are also transported. Recent studies of some neurotransmitter transporters show them to have properties of both traditional carriers and substrate-dependent ion channels, in that ion fluxes are in excess of that predicted from stoichiometric substrate fluxes. Whether these properties are comparable for all transporters, the extent to which these permeation states are independent, and whether the relationship between these two states can be regulated are not well understood. To address these questions, we expressed the Drosophila serotonin (5HT) transporter (dSERT) in Xenopus oocytes and measured both substrate-elicited ion flux and 5HT flux at various temperatures and substrate concentrations. We find that the ion flux and 5HT flux components of the transport process have a significant temperature dependence suggesting that ion flux and transmitter flux arise from a similar thermodynamically-coupled process involving large conformational changes (e.g., gating). These data are in contrast to those shown for glutamate transporters, suggesting a different permeation process for 5HT transporters. The relationship between ion flux and 5HT flux is differentially regulated by chloride and 5HT, suggesting that these permeation states are distinct. The difference in half-maximal 5HT concentration necessary to mediate ion flux and 5HT flux occurs at submicromolar 5HT concentrations suggesting that the relative participation of dSERT in ion flux and 5HT flux will be determined by the synaptic 5HT concentration.  相似文献   
86.
Ataxia-telangiectasia (A-T) is an autosomal recessive disorder caused by mutations in the ATM gene. A-T children demonstrate sensitivity to ionizing radiation, predisposition to hematological malignancies, and telangiectasias. However, the hallmark of A-T is fulminant degeneration of cerebellar Purkinje cells accompanied by a progressive ataxia with features of both cerebellar and basal ganglia dysfunction. Although the ATM gene product (ATM) is known to be involved in DNA repair, the mechanisms that link loss of ATM with neurodegeneration remain unknown. Recently, it has been suggested that abnormalities in redox status contribute to the A-T phenotype. To address this question in the nervous system, we measured reactive oxygen species (ROS) in brain regions and specific neuronal populations in ATM-/- mice. We found increased ROS levels in cerebellum and striatum but not cortex of ATM-/- mice compared to ATM+/+ mice. Confocal microscopic examination revealed elevated superoxide levels in cerebellar Purkinje cells and nigral dopaminergic neurons but not cortical neurons, thus mapping increased superoxide levels onto the neuronal populations selectively affected in A-T. These data are the first demonstration of elevated levels of ROS in neurons at risk in any genetic neurodegenerative disorder and, furthermore, suggest that ATM acts as a pro-survival signal in post-mitotic Purkinje cells and dopaminergic neurons by modifying superoxide radical handling in these selectively vulnerable neurons.  相似文献   
87.
88.
To prevent diarrheal diseases in western Kenya, CARE Kenya initiated the Water, Sanitation, and Education for Health (WASEH) Project in 1998. The project targets 72 farming and fishing communities with a total population of 43 000. Although the WASEH Project facilitated construction of shallow wells and pit latrines, the water quality still needed improvement. Consequently, in 2001, CARE implemented the Safe Water System (which consists of point-of-use water treatment with sodium hypochlorite, safe storage, and behavior change techniques) within the already established WASEH infrastructure, using existing community organizations in combination with a social marketing approach that introduced affordable products. The project has resulted in adoption rates of 33.5% for chemical water treatment and 18.5% for clay pots modified for safe water storage.  相似文献   
89.
Plasma membrane GABA transporters participate in neural signaling through re-uptake of neurotransmitter. The domains of the transporter that mediate GABA translocation and regulate transport are not well understood. In the present experiments, the N-terminal cytoplasmic domain of the GABA transporter GAT1 regulated substrate transport rates. This domain directly interacted with syntaxin 1A, a SNARE protein involved in both neurotransmitter release and modulation of calcium channels and cystic fibrosis transmembrane regulator (CFTR) chloride channels. The interaction resulted in a decrease in transporter transport rates. These data demonstrate that intracellular domains of the GABA and protein-protein interactions regulate substrate translocation, and identify a direct link between the machinery involved in transmitter release and re-uptake.  相似文献   
90.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号