全文获取类型
收费全文 | 558篇 |
免费 | 7篇 |
国内免费 | 8篇 |
专业分类
儿科学 | 6篇 |
妇产科学 | 2篇 |
基础医学 | 88篇 |
口腔科学 | 1篇 |
临床医学 | 25篇 |
内科学 | 50篇 |
皮肤病学 | 4篇 |
神经病学 | 135篇 |
特种医学 | 1篇 |
外科学 | 16篇 |
综合类 | 20篇 |
预防医学 | 36篇 |
药学 | 171篇 |
中国医学 | 8篇 |
肿瘤学 | 10篇 |
出版年
2023年 | 6篇 |
2022年 | 14篇 |
2021年 | 13篇 |
2020年 | 10篇 |
2019年 | 8篇 |
2018年 | 11篇 |
2017年 | 5篇 |
2016年 | 14篇 |
2015年 | 5篇 |
2014年 | 13篇 |
2013年 | 23篇 |
2012年 | 17篇 |
2011年 | 29篇 |
2010年 | 25篇 |
2009年 | 34篇 |
2008年 | 28篇 |
2007年 | 23篇 |
2006年 | 23篇 |
2005年 | 22篇 |
2004年 | 14篇 |
2003年 | 16篇 |
2002年 | 13篇 |
2001年 | 11篇 |
2000年 | 5篇 |
1999年 | 9篇 |
1998年 | 9篇 |
1997年 | 7篇 |
1996年 | 4篇 |
1995年 | 9篇 |
1993年 | 7篇 |
1992年 | 4篇 |
1991年 | 10篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1987年 | 8篇 |
1986年 | 9篇 |
1985年 | 6篇 |
1984年 | 5篇 |
1983年 | 5篇 |
1982年 | 10篇 |
1981年 | 10篇 |
1980年 | 3篇 |
1979年 | 17篇 |
1978年 | 11篇 |
1977年 | 4篇 |
1976年 | 5篇 |
1975年 | 7篇 |
1974年 | 6篇 |
1972年 | 6篇 |
1970年 | 2篇 |
排序方式: 共有573条查询结果,搜索用时 15 毫秒
1.
ABSTRACT Tryptophan (Trp) is not only a nutrient enhancer but also has systemic effects. Trp metabolites signaling through the well-known aryl hydrocarbon receptor (AhR) constitute the interface of microbiome-gut-brain axis. However, the pathway through which Trp metabolites affect central nervous system (CNS) function have not been fully elucidated. AhR participates in a broad variety of physiological and pathological processes that also highly relevant to intestinal homeostasis and CNS diseases. Via the AhR-dependent mechanism, Trp metabolites connect bidirectional signaling between the gut microbiome and the brain, mediated via immune, metabolic, and neural (vagal) signaling mechanisms, with downstream effects on behavior and CNS function. These findings shed light on the complex Trp regulation of microbiome-gut-brain axis and add another facet to our understanding that dietary Trp is expected to be a promising noninvasive approach for alleviating systemic diseases. 相似文献
2.
Christiana Winkler Barbara Frick Katharina Schroecksnadel Harald Schennach Dietmar Fuchs 《Food and chemical toxicology》2006,44(12):2003-2007
Antioxidant preservatives prolong the quality of food and ensure the nutritional adequacy, palatability and safety of many processed foods and beverages. Effects of sodium sulfite (E221) and sorbic acid (E200) were investigated in human peripheral blood mononuclear cells (PBMC) which were purified from blood of healthy donors. Cells were stimulated with the mitogen phytohaemagglutinin in vitro, which induces proliferation of T-cells and the production of Th1-type cytokines like interferon-γ. The latter triggers enzyme indoleamine (2,3)-dioxygenase, which degrades tryptophan, and GTP cyclohydrolase I, which leads to increased neopterin production, in monocyte-derived macrophages. Sodium sulfite and sorbic acid suppressed both these biochemical changes in a dose-dependent way (P < 0.01 at 1 mM sodium sulfite and 50 mM sorbic acid). Data demonstrate a suppressive influence of sodium sulfite and sorbic acid on the activated Th1-type immune response. 相似文献
3.
4.
Nutritional studies on rats given a choice between two diets differing in protein content have led to the proposal that brain 5-HT content regulates protein intake [2]. Pharmacologic studies under similar conditions of dietary self-selection suggest that brain 5-HT controls carbohydrate intake [41]. We tested the effect of elevating brain 5-HT via tryptophan injection (100 mg/kg) on short-term food intake and selection by rats choosing between two diets differing in protein and carbohydrate content. Under these conditions neither total food intake nor protein and carbohydrate selection were affected despite increases of 50% in brain concentrations of 5-HT and 5-HIAA. The effect of Trp administration was selective to serotonin metabolism as brain concentrations of NE, DA and DOPAC were not affected. These results suggest that alterations in brain 5-HT content which may occur following meal ingestion may not be of physiological importance in regulating nutrient intake and selection. 相似文献
5.
H. Denz B. Orth G. Weiss R. Herrmann P. Huber H. Wachter D. Fuchs 《Journal of molecular medicine (Berlin, Germany)》1993,71(1):37-41
Summary Weight loss is the main symptom of so-called tumor cachexia. The pathogenetic mechanisms underlying cachexia are poorly understood; however, it appears that enhanced formation of cytokines such as interferon- and tumor necrosis factor- are involved. In 94 patients suffering from hematological neoplasias we compared body weight changes with serum neopterin, tryptophan, and kynurenine. Biochemical changes, the formation of neopterin, the degradation of tryptophan are closely related to interferon- activity. The majority of our patients had increased neopterin and decreased tryptophan concentrations. Weight loss was seen particularly in patients with higher neopterin and lower tryptophan values. An association between higher neopterin levels and greater weight loss was apparent at study entry and during the follow-up of patients. Our data support the concept that weight loss is closely linked to endogenous interferon- activity.Abbreviations NHL
non-Hodgkin's lymphoma
- HD
Hodgkin's disease
- MM
multiple myeloma
- MGUS
monoclonal gammopathy of unknown significance
- IFN-
interferon-
- TNF-
tumor necrosis factor- 相似文献
6.
中枢性疲劳症候群临床与血清色氨酸的研究 总被引:3,自引:3,他引:0
目的:对珠海市中学生中枢性疲劳症候群的临床,患病率及与血清色氨酸的关系进行研究。方法:采用单纯随机抽样和整群一级抽样方法,对4年中学1594人进行问卷调查作为初筛,筛出有症状的部分人在医院进行以排除其它疾病为 的精查,并做血清色氨酸含量的测量,结果:临床表现自主神经症状,睡眠障碍,精神症状,推测珠海市中学生中患病率为11%,血清色氨酸含量较正常对照组低,两组有显著差异(P<0.01),结论:中枢性疲劳症候群是珠海地区中学生中的常见病,应积极于以防治;血中色氨酸含量的测定对诊断该疾病有一定的价值。 相似文献
7.
Serotonergic mechanisms of cocaine effects in humans 总被引:1,自引:0,他引:1
Sarah C. Aronson Jed E. Black Christopher J. McDougle B. Ellen Scanley George R. Heninger Lawrence H. Price Peter Jatlow Thomas R. Kosten 《Psychopharmacology》1995,119(2):179-185
The objective of this study was to investigate the role of serotonin (5-HT) in mediating the effects of cocaine in humans. To accomplish this, 12 subjects each participated in two randomized, double-blind test sessions separated by 1 week. In one session, subjects underwent acute depletion of the 5-HT amino acid precursor tryptophan (TRP), followed by a test dose of intranasal cocaine. In the other session, the cocaine test dose was preceded by sham depletion. Subject ratings of cocaine high were significantly lower following active TRP depletion than after the sham procedure. Subjects also showed an earlier but less sustained rise in self-rated nervousness during active TRP depletion. These findings are consistent with the hypothesis that 5-HT may be involved in mediating the euphorigenic and modulating the anxiogenic effects of cocaine in humans, either directly or through actions on other (e.g., dopaminergic) systems. 相似文献
8.
Identification of amino-terminal sequences contributing to tryptophan hydroxylase tetramer formation
Tryptophan hydroxylase (TPH) catalyzes the rate-limiting step in the biosynthesis of serotonin. In the rabbit, TPH exists
as a tetramer of four identical 51-kDa subunits comprised of 444 amino acids each. The enzyme consists of an amino-terminal
regulatory domain and a carboxyl-terminal catalytic domain. Previous studies demonstrated that within the carboxyl-terminus
of TPH, there resides an intersubunit binding domain (a leucine zipper) that is essential for tetramer formation. However,
it is hypothesized that a 4,3-hydrophobic repeat identified within the regulatory domain of TPH (residues 21–41) may also
be involved in macromolecular assembly. To test this hypothesis, a series of amino-terminal deletions (NΔ15, 30, 41, and 90)
were created and assessed for macromolecular structure using size-exclusion chromatography. The amino-terminal deletion NΔ15,
upstream from the 4,3-hydrophobic repeat, was capable of forming tetramers. However, when a portion of the 4,3-hydrophobic
repeat was deleted (NΔ30), a heterogeneous elution pattern of tetramers, dimers, and monomers was observed. Complete removal
of the 4,3-hydrophobic repeat (NΔ41) rendered the enzyme incapable of forming tetramers; a monomeric form predominated. In
addition, a double-point mutation (V28R-L31R) was created in the hydrophobic region of the enzyme. The introduction of two
arginines (R) at positions 28 and 31 respectively, in the helix disrupted the native tetrameric state of TPH. According to
size-exclusion chromatography analysis, the double-point mutant (V28R-L31R) formed dimers of 127 kDa. Thus, it is concluded
that there is information within the amino-terminus that is necessary for tetramer formation of TPH. This additional intersubunit
binding domain in the amino-terminus is similar to that found in the carboxyl-terminus. 相似文献
9.
Alan C. Swann B. A. Johnson C. Robert Cloninger Y. Richard Chen 《Psychopharmacology》1999,143(4):380-384
Rationale: Serotonergic (5-HT) mechanisms may be involved in impulse control (including anti-social behavior) across psychiatric syndromes.
Age of onset may differentiate alcoholics on psychopathological characteristics associated with impulse control, especially
mood disturbance, hostility, and a broad range of antisocial behaviors. Thus, there may be a predictable relationship between
markers of 5-HT function and age of onset-related characteristics. Objective: We tested the hypothesis that there would be a predictable relationship between the ratio of plasma tryptophan to large
neutral amino acids (i.e. TRYP/LNAA ratio), a marker of 5-HT function, age of onset and related psychopathological characteristics
associated with impulse control. Methods: Fifty-eight male and female DSM-IV diagnosed alcoholics attending an outpatient treatment center completing a comprehensive
psychopathological assessment, and from whom blood samples were obtained. Results: Plasma TRYP/LNAA ratio was positively correlated with symptoms of dysphoria, and negatively associated with harm avoidance
on Cloninger’s Temperament and Character Inventory. Low tryptophan availability was associated with antisocial-type personality
characteristics. Interestingly, the few (nine) subjects who had both early onset alcoholism and antisocial personality disorder
had a higher plasma tryptophan but similar TRYP/LNAA ratio to the others. Conclusions: These data suggest that a low plasma TRYP/LNAA ratio is associated with susceptibility to anxiety, antisocial-type personality
characteristics, and an early age of onset for alcoholism. In contrast, a high plasma TRYP/LNAA ratio is associated with a
later onset of alcoholism and dysphoria.
Received: 26 May 1998/Final version: 24 November 1998 相似文献
10.
Thomas Dierks Stefan Barta Lothar Demisch Klaus Schmeck Ekkehart Englert Andrea Kewitz Konrad Maurer Fritz Poustka 《Psychopharmacology》1999,146(1):101-107
Rationale: The intensity dependence of the auditory evoked potentials (AEP) has been suggested to be a specific biological marker of
central serotonergic activity. Objective: While previous studies used circumstantial evidence to support this hypothesis, we manipulated (decreased) cerebral levels
of serotonin directly by using tryptophan depletion. Methods: Twelve healthy young subjects were investigated using placebo and two different amino acid mixtures in a double blind cross
over design on three different occasions. AEPs recorded during tryptophan depletion were analyzed by dipole analysis and regional
sources using methods published in the literature. Results: For none of the mixtures a significant effect of tryptophan depletion was found. There was a trend towards reduced intensity
dependency after tryptophan depletion, especially in the right hemisphere. This reduction correlated with the amount of reduced
tryptophan in plasma. Conclusions: The results indicate, in contrast to earlier indirect studies, that the intensity dependence of AEPs is not a specific marker
of central serotonergic activity.
Received: 8 March 1999 / Final version: 25 May 1999 相似文献