全文获取类型
收费全文 | 720篇 |
免费 | 60篇 |
国内免费 | 19篇 |
专业分类
儿科学 | 2篇 |
妇产科学 | 4篇 |
基础医学 | 140篇 |
口腔科学 | 6篇 |
临床医学 | 39篇 |
内科学 | 77篇 |
皮肤病学 | 14篇 |
神经病学 | 62篇 |
特种医学 | 17篇 |
外科学 | 19篇 |
综合类 | 40篇 |
预防医学 | 26篇 |
眼科学 | 2篇 |
药学 | 284篇 |
中国医学 | 4篇 |
肿瘤学 | 63篇 |
出版年
2023年 | 8篇 |
2022年 | 7篇 |
2021年 | 21篇 |
2020年 | 27篇 |
2019年 | 14篇 |
2018年 | 23篇 |
2017年 | 26篇 |
2016年 | 23篇 |
2015年 | 30篇 |
2014年 | 38篇 |
2013年 | 85篇 |
2012年 | 30篇 |
2011年 | 44篇 |
2010年 | 42篇 |
2009年 | 28篇 |
2008年 | 41篇 |
2007年 | 29篇 |
2006年 | 25篇 |
2005年 | 25篇 |
2004年 | 29篇 |
2003年 | 31篇 |
2002年 | 18篇 |
2001年 | 11篇 |
2000年 | 14篇 |
1999年 | 13篇 |
1998年 | 11篇 |
1997年 | 15篇 |
1996年 | 9篇 |
1995年 | 11篇 |
1994年 | 12篇 |
1993年 | 3篇 |
1992年 | 10篇 |
1991年 | 6篇 |
1990年 | 1篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1987年 | 7篇 |
1986年 | 3篇 |
1985年 | 5篇 |
1984年 | 7篇 |
1983年 | 1篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 2篇 |
排序方式: 共有799条查询结果,搜索用时 843 毫秒
1.
Byron H Hartman Toshinori Hayashi Branden R Nelson Olivia Bermingham-McDonogh Thomas A Reh 《Developmental dynamics》2007,236(10):2875-2883
Notch mediates the process of lateral inhibition that controls the production of hair cells in the inner ear. Hair cells are known to express Notch ligands Dll1 and Jag2, which signal through Notch1 in adjacent supporting cells. However, recent genetic and pharmacological studies indicate that the level of Notch-mediated lateral inhibition is greater than can be accounted for by Dll1 and Jag2. Here, we report that another Notch ligand, Dll3, is expressed in developing hair cells, in a pattern that overlaps that of Dll1 and Jag2. We analyzed the cochleae of Dll3(pu) mutant mice, but did not detect any abnormalities. However, earlier studies have demonstrated that there is functional redundancy among Notch ligands in cochlear development and loss of one ligand can be at least partially compensated for by another. Thus Dll3 may play a role in lateral inhibition similar to that of Dll1 and Jag2. 相似文献
2.
Production and detection of monoclonal anti-idiotype antibodies directed against a monoclonal anti-beta-adrenergic ligand antibody 总被引:2,自引:0,他引:2
A new method has been developed to raise monoclonal anti-idiotypic antibodies. Monoclonal anti-idiotypic antibodies were obtained by fusion of NS-1 myeloma cells with splenocytes of mice immunised by intravenous injections of fixed hybridoma cells bearing a monoclonal antibody specific for beta-adrenergic ligands. New screening tests were developed to analyse the resulting hybridoma supernatants for different anti-idiotypic properties. Among 23 hybridoma supernatants recognising the idiotype, 6 were found to inhibit hapten binding and 3 of these recognised beta-adrenergic receptors. 相似文献
3.
Yu. B. Lishmanov B. Yu. Kondrat’ev L. N. Maslov N. V. Naryzhnaya 《Bulletin of experimental biology and medicine》1997,123(2):130-132
Acute cold exposure (−20°C, 4 h) induces a transient decrease in the ventricular fibrillation threshold without morphological
and radionuclide signs of irreversible damage to cardiomyocytes. The agonist of μ-receptors DAGO, which reduces adrenoreactivity
of the myocardium, prevents the decrease in the ventricular fibrillation threshold induced by acute cold exposure.
Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 123, No. 2, pp. 154–157, February, 1997 相似文献
4.
Gaenko GP Kozlov AM Saprykina NS Dorotnikova EB Khaidukov SV Molotkovskii YG 《Bulletin of experimental biology and medicine》2002,134(4):382-384
We studied adhesive properties and physiological activity in vivo of cells from Lewis lung carcinoma and its metastases. These cells differed in tumorogenic activity and metastatic potential in the syngeneic system. In vivo non-metastasizing cells are characterized by a lower content of surface lectins to tetrasaccharides SiaLex [Neu5Ac2-3Gal1-4(Fuc1-3) GlcNAc] and SiaLea [Neu5Ac2-3Gal1-3(Fuc1-4)GlcNAc] and trisaccharide HSO3Lex [HSO32-3Gal1-4(Fuc1-3)GlcNAc] compared to cells forming metastases in the syngeneic system. Metastatic cells with low tumorogenic activity weakly expressed lectins to disaccharide ligands 6-SiaLac [Neu5Ac2-6Gal1-4Glc], 6-HSO3LacNAc, and A-di [GalNAc 1-3Gal] and trisaccharides H-type 1 [Fuc1-2Gal1-3GlcNAc and Lex [Fuc1-3(Gal 1-4)GlcNAc] compared to cells that initiated tumor formation in the syngeneic system (similarly to transplanted tumors). We hypothesized that cell receptors to these carbohydrate determinates are involved in the development and growth of primary tumors, while lectins to SiaLex, SiaLea, and HSO3Lex play a role in the progress of tumor process and metastasizing. 相似文献
5.
Gertrud Koch Klaus Wiedemann Hansjörg Teschemacher 《Naunyn-Schmiedeberg's archives of pharmacology》1985,331(4):351-354
Summary Opioid activities of human -casomorphin-4,-5,-7 and -8 and, for comparison, of the corresponding bovine -casomorphins were studied in the guinea-pig ileum preparation. Binding parameters, i.e. K
d
-values and binding site concentrations, for the interaction of human and bovine -casomorphins with opioid receptors in rat brain homogenates were determined in inhibition experiments, using [3H]-(d-Ala2, MePhe4, Gly-ol5)enkephalin, [3H]-(d-Ala2, d-Leu5)enkephalin and [3H]ethylketazocin as -, - and -opioid receptor ligands. Analysis of binding data was performed using a non-linear curve fitting program. All -casomorphins examined displayed opioid activity. The affinity was highest for -receptors, less so for -receptors and lowest for -receptors. It is suggested that human -casomorphins might play a role as food hormones. 相似文献
6.
Previous research has found that drugs with affinity for (benzodiazepine) sites differ in their abilities to produce tolerance and dependence. The present study therefore investigated the effects of ligands of (BZ) sites in rats that had been rendered tolerant to a benzodiazepine. Two experiments were carried out in separate groups of rats. Behavioral changes induced by chronic infusion of triazolam (3 mg/kg/day, SC, for 14 days) via osmotic pumps were studied in animals trained on a fixed ratio 10 schedule of food presentation. Control animals were implanted with pumps containing the vehicle. Test drugs were administered IP using cumulative dosing. In one experiment triazolam decreased response rates on days 1, 2 and 3 after implantation of the pumps and tolerance developed to this depressant effect. In the other experiment, vehicle and triazolam treated rats differed in their responding during chronic infusion but differences were not statistically significant on any particular day. Flumazenil (3.0–30 mg/kg) greatly decreased rates of responding on day 11 in triazolam treated rats. This effect may represent a precipitated withdrawal syndrome. However, no withdrawal effects on operant performance were observed upon pump removal. Chronic infusion of triazolam did not affect the sensitivity of rats to alpidem on day 11 (10–100 mg/kg) whereas it abolished the stimulant effect of bretazenil (0.1–1.0 mg/kg). Chronic triazolam treatment produced tolerance to the depressant effects of triazolam (1.0–3.0 mg/kg), lorazepam (0.3–3.0 mg/kg) and zopiclone (10 mg/kg) but no tolerance to those of CL 218,872 (3.0–30 mg/kg) and zolpidem (0.3–3.0 mg/kg) when tested 3–14 days after pump removal. Differences between compounds highlighted with this model are in agreement with previous observations that these agents possess different pharmacological profiles and different potentials to induce tolerance and dependence. 相似文献
7.
B Beer C A Klepner A S Lippa R F Squires 《Pharmacology, biochemistry, and behavior》1978,9(6):849-851
SQ 65,396, a clinically active anti-anxiety agent, enhanced the binding of 3H-diazepam at 1.5 nM. This effect was due to an increase in the affinity for the ligand, without a change in the number of 3H-diazepam binding sites. This action of SQ 65,396 may mediate its anti-anxiety effects by affecting the action of an endogenous modulator of the "benzodiazepine receptor." Several other substances and treatments increase the affinity of 3H-diazepam for its receptors by mechanisms which may be related to the effect produced by SQ 65,396. 相似文献
8.
阿片类前体药物的研究进展 总被引:2,自引:0,他引:2
从提高代谢稳定性、膜通透性、延长作用时效、定位于脑内的化学传递系统、去除苦味、减少血浆蛋白结合率等6个方面介绍了近年来国内外有关阿片类前体药物的应用,对现有镇痛药物的研究和开发有一定的参考价值. 相似文献
9.
Tomoya Hirota Hiroto Tsuboi Mana Iizuka-Koga Hiroyuki Takahashi Hiromitsu Asashima Masahiro Yokosawa 《Modern rheumatology / the Japan Rheumatism Association》2017,27(3):457-465
Objective: To investigate the effects of transgenic rice seeds expressing the altered peptide ligand (APL) of human glucose-6-phosphate-isomerase (hGPI325–339) in mice model of GPI-induced arthritis (GIA).Methods: We generated transgenic rice expressing T-cell epitope of hGPI325–339 and APL12 contained in the seed endosperm. The transgenic rice seeds were orally administered prophylactically before the induction of GIA. The severity of arthritis and titers of serum anti-GPI antibodies were evaluated. We examined for IL-17 production in splenocytes and inguinal lymph node (iLN) cells, and analyzed the expression levels of functional molecules in splenocytes.Results: Prophylactic treatment of GIA mice with APL12 transgenic (APL12-TG) rice seeds significantly reduced the severity of arthritis and titers of serum anti-GPI antibodies compared with non-transgenic (Non-TG) rice-treated mice. APL12-TG and hGPI325–339 transgenic (hGPI325–339-TG) rice seeds improved the histopathological arthritis scores and decreased IL-17 production compared with non-TG rice-treated mice. APL12-TG rice-treated GIA mice showed upregulation of Foxp3 and GITR protein in CD4?+?CD25?+?Foxp3+?cells in the spleen compared with non-TG rice- and hGPI325–339-TG rice-treated mice.Conclusion: APL12-TG rice seeds improved the severity of GIA through a decrease in production of IL-17 and anti-GPI antibodies via upregulation of Foxp3 and GITR expression on Treg cells in spleen. 相似文献
10.
《Expert opinion on therapeutic patents》2013,23(9):1171-1196
Importance of the field: Among the GPCR subclasses that have been discovered to date, 5-HT receptors are especially attractive as key biological targets with enormous clinical importance. In particular, during the last decade, the 5-HT6 receptor has gained increasing attention due to extensive cellular functions. It has also been suggested that its activity can be mediated by inverse agonists.Areas covered in this review: Summarizing the points listed above, the current review primarily focuses on patent literature within the title field, evolution and trends that have not yet been covered in such depth in other published papers.What the reader will gain: To obtain a clear understanding of the situation and dynamics within the field of 5-HT6 ligands, having an obvious pharmaceutical potential in terms of related patents, we provide a comprehensive search through several key patent collections. We have covered promising small molecule compounds which are being evaluated in different clinical trials as well as drugs currently available in the pharmaceutical market. In addition, readers will gain a deep insight into the patent specification, geographic distribution, tendency and patent holders presented.Take home message: Several of 5-HT6-targeted compounds are reasonably regarded as powerful drug candidates for the treatment of a range of neuropathological disorders, including Alzheimer's disease and Huntington's disease. 相似文献