全文获取类型
收费全文 | 9105篇 |
免费 | 704篇 |
国内免费 | 48篇 |
专业分类
耳鼻咽喉 | 55篇 |
儿科学 | 228篇 |
妇产科学 | 118篇 |
基础医学 | 1640篇 |
口腔科学 | 75篇 |
临床医学 | 996篇 |
内科学 | 1932篇 |
皮肤病学 | 113篇 |
神经病学 | 881篇 |
特种医学 | 376篇 |
外科学 | 1403篇 |
综合类 | 92篇 |
一般理论 | 1篇 |
预防医学 | 695篇 |
眼科学 | 139篇 |
药学 | 559篇 |
中国医学 | 17篇 |
肿瘤学 | 537篇 |
出版年
2022年 | 66篇 |
2021年 | 100篇 |
2020年 | 92篇 |
2019年 | 167篇 |
2018年 | 163篇 |
2017年 | 128篇 |
2016年 | 142篇 |
2015年 | 183篇 |
2014年 | 228篇 |
2013年 | 356篇 |
2012年 | 468篇 |
2011年 | 549篇 |
2010年 | 346篇 |
2009年 | 316篇 |
2008年 | 539篇 |
2007年 | 534篇 |
2006年 | 529篇 |
2005年 | 620篇 |
2004年 | 607篇 |
2003年 | 711篇 |
2002年 | 676篇 |
2001年 | 85篇 |
2000年 | 67篇 |
1999年 | 103篇 |
1998年 | 173篇 |
1997年 | 141篇 |
1996年 | 109篇 |
1995年 | 98篇 |
1994年 | 110篇 |
1993年 | 71篇 |
1992年 | 67篇 |
1991年 | 67篇 |
1990年 | 64篇 |
1989年 | 57篇 |
1988年 | 60篇 |
1987年 | 56篇 |
1986年 | 58篇 |
1985年 | 52篇 |
1984年 | 63篇 |
1983年 | 60篇 |
1982年 | 69篇 |
1981年 | 67篇 |
1980年 | 62篇 |
1979年 | 41篇 |
1978年 | 51篇 |
1977年 | 47篇 |
1976年 | 52篇 |
1975年 | 35篇 |
1974年 | 48篇 |
1973年 | 28篇 |
排序方式: 共有9857条查询结果,搜索用时 15 毫秒
21.
Internalization of sst2, sst3, and sst5 receptors: effects of somatostatin agonists and antagonists. 总被引:4,自引:0,他引:4
Renzo Cescato Stefan Schulz Beatrice Waser Véronique Eltschinger Jean E Rivier Hans-Jürgen Wester Michael Culler Mihaela Ginj Qisheng Liu Agnes Schonbrunn Jean Claude Reubi 《Journal of nuclear medicine》2006,47(3):502-511
The uptake of radiolabeled somatostatin analogs by tumor cells through receptor-mediated internalization is a critical process for the in vivo targeting of tumoral somatostatin receptors. In the present study, the somatostatin receptor internalization induced by a variety of somatostatin analogs was measured with new immunocytochemical methods that allow characterization of trafficking of the somatostatin receptor subtype 2 (sst2), somatostatin receptor subtype 3 (sst3), and somatostatin receptor subtype 5 (sst5) in vitro at the protein level. METHODS: Human embryonic kidney 293 (HEK293) cells expressing the sst2, sst3, or the sst5 were used in a morphologic immunocytochemical internalization assay using specific sst2, sst3 and sst5 antibodies to qualitatively and quantitatively determine the capability of somatostatin agonists or antagonists to induce somatostatin receptor internalization. In addition, the internalization properties of a selection of these agonists have been compared and quantified in sst2-expressing CHO-K1 cells using an ELISA. RESULTS: Agonists with a high sst2-binding affinity were able to induce sst2 internalization in the HEK293 and CHO-K1 cell lines. New sst2 agonists, such as Y-DOTA-TATE, Y-DOTA-NOC, Lu-DOTA-BOC-ATE (where DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; TATE is [Tyr3, Thr8]-octreotide; NOC is [1-NaI3]-octreotide; and BOC-ATE is [BzThi3, Thr8]-octreotide), iodinated sugar-containing octreotide analogs, or BIM-23244 were considerably more potent in internalizing sst2 than was DTPA-octreotide (where DTPA is diethylenetriaminepentaacetic acid). Similarly, compounds with high sst3 affinity such as KE108 were able to induce sst3 internalization. In sst2- or sst3-expressing cell lines, agonist-induced receptor internalization was efficiently abolished by sst2- or sst3-selective antagonists, respectively. Antagonists alone had no effect on sst2 or sst3 internalization. We also showed that somatostatin-28 and somatostatin-14 can induce sst5 internalization. Unexpectedly, however, potent sst5 agonists such as KE108, BIM-23244, and L-817,818 were not able to induce sst5 internalization under the same conditions. CONCLUSION: Using sensitive and reproducible immunocytochemical methods, the ability of various somatostatin analogs to induce sst2, sst3, and sst5 internalization has been qualitatively and quantitatively determined. Whereas all agonists triggered sst2 and sst3 internalization, sst5 internalization was induced by natural somatostatin peptides but not by synthetic high-affinity sst5 agonists. Such assays will be of considerable help for the future characterization of ligands foreseen for nuclear medicine applications. 相似文献
22.
We consider the problem of detection of modifier genes that lead to variations in a disease‐related continuous variable (DRCV), such as the age of onset or a measure of disease severity, in a strategy of candidate genes. We propose a novel method, the ordered transmission disequilibrium test (OTDT), to test for a relation between the clinical heterogeneity expressed by a DRCV and marker genotypes of a candidate gene. The OTDT applies to trio families with one patients and his parents, all three genotyped at a bi‐allelic marker M. The OTDT aims to find a critical value of the DRCV which separates the sample of families in two subsamples in which the transmission rates are significantly different. We investigate the power of the method by simulations under various genetic models and covariate distributions and compare it with a linear regression analysis. Genet. Epidemiol. 2008. ©2008 Wiley‐Liss, Inc. 相似文献
23.
24.
We have investigated the distribution of vasopressin binding sites in the brain of male and female adult mice using a radio-iodinated ligand and film autoradiography. Vasopressin receptors were uncovered in various regions of the brain including the basal nucleus of Meynert, the substantia innominata, the hypothalamic paraventricular nucleus, the substantia nigra pars compacta and the hypoglossal nucleus. A sex-related difference in the expression of vasopressin receptors was seen in the medial preoptic area/anterior hypothalamus corresponding to the rat sexually dimorphic nucleus in the rat and in the hypothalamic mammillary nuclei. In both structures the autoradiographic labeling is more intense in females than in males. These observations confirm that vasopressin binding sites are present in the hypothalamic preoptic area of most species examined so far and that sex-related expression of neuropeptide receptors could trigger sex-related behavioral differences. 相似文献
25.
An experimental study was conducted in guinea pigs for the predictive assessment of the beryllium alloy hazard in occupational exposure of the skin to beryllium compounds. Guinea pigs were sensitized to beryllium sulfate according to the maximized Magnusson and Kligman test, and challenged with beryllium alloys and metallic copper, beryllium and aluminum samples. Results showed a delayed skin hypersensitivity reaction in 30 to 60% of pre-sensitized guinea pigs challenged with copper-beryllium alloys and aluminum-beryllium alloy. An inflammatory follicular reaction was induced by copper in both controls and pre-sensitized guinea pigs. 相似文献
26.
Joey C Eisenmann Peter T Katzmarzyk Louis Perusse Claude Bouchard Robert M Malina 《The Journal of adolescent health》2003,33(3):147-153
PURPOSE: To examine the association between estimated daily energy expenditure and blood lipids in a sample of adolescents. METHODS: The sample consisted of 415 males and 356 females aged 10-19 years, mainly French Canadian, recruited from the greater Quebec City area through the media as part of Phase I of the Quebec Family Study. Estimates of daily energy expenditure (DEE) were obtained with a 3-day physical activity record. Blood lipids were measured by standard procedures. The sample was stratified into three activity groups (least active, less than 25th percentile of DEE; moderately active, 25-74th percentile of DEE; and most active, 75th percentile or greater of DEE), and also by clinical cutpoints for blood lipids. Analysis of covariance, controlling for age and fatness, was conducted to compare blood lipids within gender across activity groups. Logistic regression analysis, controlling for age and fatness, was used to estimate the relative risk of being classified with an undesirable level of a blood lipid parameter on the basis of the DEE. RESULTS: Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were not significantly different across activity groups in males or females. High-density lipoprotein cholesterol (HDL-C) was significantly different across activity groups in males (p <.05) and females (p <.05), but the pattern of variation was different between genders. In males, the TC/HDL-C and LDL-C/HDL-C ratios decreased between the moderately active and most active groups (p <.05). Significant differences remained when subcutaneous fatness was considered as a covariate. The results from logistic regression analysis indicated that the odds ratios for low HDL-C levels was significant only in low DEE girls (odds ratio 2.83) compared with high DEE girls. CONCLUSIONS: The results suggest that increased energy expenditure and physical activity are associated with higher levels of HDL-C in adolescents of both sexes. 相似文献
27.
Gustave Savourey Nathalie Garcia Jean Pierre Caravel Claude Gharib Nadine Pouzeratte Serge Martin Jacques Bittel 《European journal of applied physiology》1997,77(1-2):37-43
High altitude residence is known to modify body biochemistry and hormone status. However, the effects of such a sojourn on these status observed at sea level both immediately and later after return are not as well established as are the effects of an intermittent acclimation. The aim of this study was therefore to investigate these changes. To achieve our objectives, nine subjects received intermittent acclimation at low pressure in a barometric chamber (8?h daily for 5 days, day 1 at 4500 m, day 5 at 8500 m) before an expedition to the Himalayas. Hormonal and biochemical changes were studied using samples of venous blood taken at sea level before and after acclimation, after return from the expedition and 1 and 2 months after descent. Concentrations of thyroid hormones, adrenaline, noradrenaline (NA), hormones of hydromineral metabolism (aldosterone, renin, arginine vasopressin, atrial natriuretic peptide) as well as prolactin, cortisol, insulin and endothelin 1 were measured. Biochemical measurements made were plasma osmolality, and concentrations of glucose, total cholesterol, total proteins, pre-albumin, transferrin, complement 3C, apolipoproteins A1 and B and serum iron. Acclimation induced no alteration in hormone (except for NA with increases of about 1.5, fold P<0.05) and biochemistry data. After the expedition, hormone responses were characterized by a higher total triidothyronine concentration (+18%, P<0.05) while other hormones did not vary. A linear relationship was found between thyroid-stimulating-hormone and body mass changes after the expedition (r=0.67, P<0.05). The observed increased concentrations of plasma proteins and total cholesterol (P<0.05) could be related to the restoration of lean body mass. At 1 and 2 months after return, no changes in hormones were observed but a significant decrease in transferrin concentration was noticed. The higher serum iron concentration reported after 1 month (P<0.05) could have been the result of a physiological haemolysis. It was concluded that both acclimation and the expedition in the Himalayas affected hormone status and body biochemistry status even though the observed changes were slight and rapidly reversed. 相似文献
28.
Postural Control of Three-Dimensional Prehension Movements 总被引:7,自引:0,他引:7
29.
Gabriel Gandolfo Gerard Lambeau Michel Lazdunski Claude Gottesmann 《Basic & clinical pharmacology & toxicology》1996,78(5):341-347
Abstract: Three phospholipase A2 (PLA2s), OS1 and OS1 purified from the taipan snake venom Oxyuranus scutellatus scutellatus and bee venom PLA2 were injected to rats by the intracerebroventricular route. OS1 showed no sign of neurotoxicity at doses at which OS2 and bee venom PLA2 produced multiform dose-dependent behavioural effects including motor disturbances (stereotyped movements), compulsive scratching, convulsions and breathing difficulties. EEG recordings showed at the very time when the animal was motionless the induction of several episodes of a low frequency hippocampal theta rhythm, index of long-term changes in synaptic neuroplasticity. Spike-wave discharges were also produced but the occurrence was not systematic. These seizures were often accompanied with behavioural convulsions. Blockers of NMDA receptors and drugs modifying the GABAergic transmission could not abolish the neurotoxic effects of PLA2s except for diazepam (10 mg/kg intraperitoneally) that prevented only OS2-induced disturbances. Blockers of L-type Ca2+ channels and K+ channel openers were also without effect. The toxicity of OS2 and bee venom PLA2 is probably due to their initial specific binding to their neuronal receptor sites. 相似文献
30.
J. R. Claude 《Comparative clinical pathology》1993,3(3):174-177
The aim of this paper is to emphasize the necessity of an international harmonisation of the guidelines in toxicology for
the safety evaluation of pharmaceutical products, and the role of the International Conference on Harmonization (ICH). The
organisation of the working-groups and the choice of the topics are descibed, and an overview of the achievement and on the
difficulties encountered for this purpose is presented, some months before the ICH2 meeting in Orlando (USA).
Originally presented at ECCP 93. 相似文献