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   26908篇
  免费   2197篇
  国内免费   829篇
耳鼻咽喉   143篇
儿科学   386篇
妇产科学   305篇
基础医学   3394篇
口腔科学   219篇
临床医学   1933篇
内科学   5435篇
皮肤病学   426篇
神经病学   1232篇
特种医学   262篇
外国民族医学   1篇
外科学   2187篇
综合类   2325篇
现状与发展   7篇
预防医学   1475篇
眼科学   256篇
药学   5481篇
  13篇
中国医学   763篇
肿瘤学   3691篇
  2024年   97篇
  2023年   742篇
  2022年   1242篇
  2021年   1562篇
  2020年   1425篇
  2019年   1146篇
  2018年   1012篇
  2017年   1217篇
  2016年   1119篇
  2015年   1261篇
  2014年   1593篇
  2013年   2632篇
  2012年   1353篇
  2011年   1644篇
  2010年   1111篇
  2009年   1097篇
  2008年   1145篇
  2007年   1066篇
  2006年   1042篇
  2005年   807篇
  2004年   667篇
  2003年   659篇
  2002年   519篇
  2001年   422篇
  2000年   352篇
  1999年   322篇
  1998年   284篇
  1997年   255篇
  1996年   231篇
  1995年   197篇
  1994年   196篇
  1993年   155篇
  1992年   137篇
  1991年   134篇
  1990年   117篇
  1989年   116篇
  1988年   102篇
  1987年   93篇
  1986年   70篇
  1985年   92篇
  1984年   90篇
  1983年   52篇
  1982年   77篇
  1981年   49篇
  1980年   50篇
  1979年   48篇
  1978年   40篇
  1977年   28篇
  1976年   26篇
  1975年   10篇
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
1.
2.
Pyroglutamyl, proline-rich oligopeptides, classically referred to as bradykinin-potentiating peptides (BPPs) are found in Bothrops jararaca venom, and are naturally occurring inhibitors of the somatic angiotensin-converting enzyme (ACE). The chemical and pharmacological properties of these peptides were essential for the development of captopril, the first active site directed inhibitor of ACE, currently used to treat human hypertension. ACE is a complex ectoenzyme of the vascular endothelium, possessing two catalytic sites, performing diverse specific roles. Recent advances concerning novel features of BPPs revealed that they might still contribute to a better understanding of the cardiovascular physiology and pathology. The molecular biology of the BPPs revealed that they are part of two distinct C-type natriuretic peptide precursors found in the venom gland and the brain of B. jararaca, each containing seven BPPs. In situ hybridization studies detected the presence of the corresponding mRNA precursor in snake brain regions correlated with neuroendocrine functions, such as the ventro-medial hypothalamus, the paraventricular nuclei, the paraventricular organ, and the subcommissural organ. In this article we discuss the large variety of homologous BPPs in B. jararaca venom and brain, its significance, and whether the BPPs could represent novel endogenous neuropeptides.  相似文献   
3.
Abstract: We have designed and synthesized a new series of azapeptides which act as potential inhibitors of cathepsin B and/or cathepsin K. Their structures are based upon the inhibitory sites of natural cysteine protease inhibitors, cystatins. For the synthesized azapeptides, the equilibrium constants for dissociation of inhibitor–enzyme complex, Ki, were determined. Comparison of these values indicated that all of the azainhibitors act much stronger toward cathepsin B. Z‐Arg‐Leu‐His‐Agly‐Ile‐Val‐OMe ( 7 ) proved to be approximately 500 times more potent for cathepsin B than for cathepsin K. To be able to explain the obtained experimental values we used the molecular dynamics procedures to analyze the interactions between cathepsin B and compound 7 . We also determined the structure of the most potent and selective cathepsin B azainhibitor by means of NMR studies and theoretical calculations. In this report, we describe SAR studies of azapeptide inhibitors indicating the influence of the conformational flexibility of the examined compounds on inhibition of cathepsins B and K.  相似文献   
4.
The greatest benefit of immunosuppression minimization for children may lie in improving patient morbidity, by the elimination of the inherent side effects of steroid and calcineurin inhibitors (CNI). The newer generation of powerful induction and maintenance immunosuppressants offers an option for selected immunosuppression minimization strategies, some of which have been shown to also reduce graft morbidity. Steroid minimization and avoidance in single-center uncontrolled trials have shown early promise and the availability of data from an ongoing randomized, prospective, controlled trial of steroid avoidance in children will provide necessary data to support a practice change for steroid elimination in children. Calcineurin inhibitor minimization and addition of mycophenolate mofetil (MMF) or sirolimus have shown variable improvements in renal function, though suboptimal efficacy and safety with the currently proposed regimes have limited their application. Randomized, prospective studies of steroid and calcineurin inhibitor minimization and/or avoidance are warranted to clearly confirm the short and long-term safety and efficacy of alternative immunosuppression combinations. Linked pharmacokinetic and mechanistic studies within these trials will allow for optimizing drug dosing and monitoring. This article reviews published experience to date with steroid and calcineurin minimization in pediatric renal transplantation and discusses the risks and benefits of these approaches.  相似文献   
5.
6.
7.
6-[(4-Quinolinyl)oxy]hexanoic acids and the corresponding esters were designed and synthesized as inhibitors of the production of arachidonic acid metabolites. The inhibitory activities were assayed in vitro by evaluation of serum leukotriene B4 and thromboxane B2 production. While all 6-[(4-quinolinyl)oxy]hexanoic acids and their esters proved to be inactive, the N-alkyl-4-quinolones, obtained as by-products in their synthesis, were found to be a new class of leukotriene biosynthesis inhibitors.  相似文献   
8.
Summary Rats were treated with desipramine 5mg/kg, nomifensine 10mg/kg, zimelidine 25 mg/kg or with 0.9% sodium chloride once a day during the second and third weeks after birth, and brain stem, caudate/putamen and cortical monoamines, and caudate/putamen dopamine D1 (3[H]SCH 23390) and D2 (3[H]spiroperidol) receptor binding were measured when rats were at two months of age. In the brain stem, the concentration of 3-methoxy-4-hydroxy-phenyl glycol was increased in nomifensine rats and the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in zimelidine rats. In the caudate/putamen, the concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid and the ratio of homovanillic acid to dopamine were increased in desipramine rats; neither3[H]SCH 23390 nor3[H]spiroperidol binding were affected by any of the three monoamine uptake inhibiting antidepressants studied. In the cortex, the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in desipramine and zimelidine rats. The findings suggest that desipramine but not nomifensine increases the metabolism of dopamine in the caudate/ putamen and nomifensine but not desipramine increases the metabolism of norepinephrine in the brain stem, and furthermore that the metabolism of serotonin is affected by desipramine as well as by zimelidine. It is possible that also treatment of women with these drugs during late pregnancy causes long-lasting changes in the brain of human fetus.  相似文献   
9.
The role of proteolytic enzymes in the hCG-induced increase in testicular vasopermeability and neutrophil extravasation was studied using protease inhibitors. An intra-testicular injection of hCG together with incubation medium conditioned by polymorphonuclear leucocytes (PMNs) caused a significant increase in vasopermeability and a coincident extravasation of PMN's from the postcapillary venules in the rat testis. When p-aminobenzamidine, a serine protease inhibitor which inhibits urokinase-type plasminogen activator, was administered together with hCG in the incubation medium, both the permeability increase and PMN extravasation were prevented. Aprotinin, another serine protease inhibitor, and Eglin C, a specific neutrophil elastase and cathepsin G inhibitor were, however, without effect. None of these inhibitors caused any non-specific vascular effects in the testis at the concentrations used. These results support the concept that the hCG-induced increase in vasopermeability in the rat testis is related to extravasation of PMNs and suggest that urokinase-type plasminogen activator is involved in migration of these cells through the postcapillary venular walls.  相似文献   
10.
In search of potential drugs for the treatment of estrogen- and androgen-dependent cancer as well as the prophylaxis of metastases, tetralones, tetralins, and dihydronaphthalenes bearing a OCH3 substituent at the benzene nucleus and an imidazol-4-yl, imidazol-1-yl, or 1,2,4-triazol-1-yl substituent in 2-position were synthesized with and without C1-spacer between the rings (compounds 2 – 26 ). The compounds were tested in vitro for inhibition of the three target enzymes P450 arom (human placental microsomes), P450 17 (rat testicular microsomes), and P450 TxA2 (citrated human whole blood). To examine selectivity, some compounds were further tested in vitro for inhibition of P450 18 (bovine adrenal mitochondria), P450 see (bovine adrenal mitochondria) and corticoid formation (aldosterone, corticosterone; ACTH stimulated rat adrenal tissue). In vivo, selected compounds were examined in Sprague Dawley rats regarding P450 TxA2 inhibition, reduction of plasma testosterone concentration, antiuterotrophic activity (inhibition of the uterotrophic activity of androstenedione), reduction of plasma estradiol concentration (pregnant mares' serum gonadotropin-primed rats), and mammary tumor inhibiting activity (dimethylbenzanthracene-induced tumor; pre- and postmenopausal model). In the series of imidazol-4-yl compounds, which represent a novelty in the field of azole inhibitors of steroidogenic P450 enzymes, strong inhibitors of P450 arom and/or P450 17 were found: 7-OCH3-2-(imidazol-4-ylmethylene)-1-tetralone ( 4 ) and 7-OCH3-2-(imidazol-4-ylmethyl)-tetralin ( 12 ) are among the most potent inhibitors of P450 arom in vitro known so far. Compound 4 is a selective inhibitor, whereas 12 shows in addition strong inhibition of P450 17. In contrast to 12 , the 6-OCH3 derivative (compound 11 ) is a selective inhibitor of P450 17, being 50 times more potent than ketoconazole. Some imidazol-1-yl compounds show a marked inhibition of P450 TxA2: 2-(imidazol-1-ylmethyl)-1-tetralone ( 13 ) is a selective inhibitor of P450 TxA2, whereas 7-OCH3-2-(imidazol-1-ylmethyl)-tetralin ( 17 ) as well as 2-(imidazol-1-ylmethyl)-tetralin ( 16 ) and 7-OCH3-2-imidazol-1-yl-3,4-dihydronaphthalene ( 25 ) additionally show strong inhibition of P450 arom and P450 17. Regarding the other steroidogenic P450 enzymes as well as corticosterone formation, the compounds show only little inhibitory activity. Aldosterone formation, however, is inhibited at low concentrations. Nevertheless, 4 and 12 are more selective, i.e. inhibit aldosterone synthesis less than the well known inhibitor of P450 arom fadrozole. The compounds show activity in the aforementioned in vivo tests.  相似文献   
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