全文获取类型
收费全文 | 1441篇 |
免费 | 172篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 27篇 |
妇产科学 | 7篇 |
基础医学 | 198篇 |
口腔科学 | 29篇 |
临床医学 | 270篇 |
内科学 | 190篇 |
皮肤病学 | 12篇 |
神经病学 | 44篇 |
特种医学 | 61篇 |
外国民族医学 | 2篇 |
外科学 | 59篇 |
综合类 | 7篇 |
预防医学 | 110篇 |
眼科学 | 16篇 |
药学 | 531篇 |
中国医学 | 5篇 |
肿瘤学 | 44篇 |
出版年
2022年 | 12篇 |
2021年 | 12篇 |
2019年 | 9篇 |
2017年 | 11篇 |
2016年 | 12篇 |
2015年 | 27篇 |
2014年 | 14篇 |
2013年 | 22篇 |
2012年 | 33篇 |
2011年 | 37篇 |
2010年 | 19篇 |
2009年 | 37篇 |
2008年 | 64篇 |
2007年 | 75篇 |
2006年 | 52篇 |
2005年 | 60篇 |
2004年 | 52篇 |
2003年 | 52篇 |
2002年 | 69篇 |
2001年 | 85篇 |
2000年 | 77篇 |
1999年 | 75篇 |
1998年 | 29篇 |
1997年 | 22篇 |
1996年 | 27篇 |
1995年 | 21篇 |
1994年 | 28篇 |
1993年 | 23篇 |
1992年 | 49篇 |
1991年 | 52篇 |
1990年 | 40篇 |
1989年 | 45篇 |
1988年 | 46篇 |
1987年 | 49篇 |
1986年 | 30篇 |
1985年 | 26篇 |
1984年 | 31篇 |
1983年 | 21篇 |
1982年 | 19篇 |
1981年 | 15篇 |
1980年 | 13篇 |
1979年 | 9篇 |
1978年 | 7篇 |
1977年 | 7篇 |
1976年 | 8篇 |
1975年 | 12篇 |
1974年 | 12篇 |
1973年 | 11篇 |
1972年 | 7篇 |
1971年 | 10篇 |
排序方式: 共有1614条查询结果,搜索用时 0 毫秒
81.
Leyssen P Charlier N Lemey P Billoir F Vandamme AM De Clercq E de Lamballerie X Neyts J 《Virology》2002,293(1):125-140
We recently developed a model for flavivirus infection in mice and hamsters using the Modoc virus (MODV), a flavivirus with no known vector (P. Leyssen, A. Van Lommel, C. Drosten, H. Schmitz, E. De Clercq, and J. Neyts, 2001, Virology 279, 27-37). We now present the coding and noncoding sequence of MODV. The Modoc virus genome was determined to be 10,600 nucleotides in length with a single open reading frame extending from nucleotides 110 to 10,234, encoding 3374 amino acids. The deduced gene order of the single open reading frame is C-prM-E-NS1-NS2A-NS2B-NS3-NS4A-NS4B-NS5, which is exactly the same as that of the mosquito- and tick-borne flaviviruses. It is flanked by a 5'- and 3'-untranslated region (UTR) of 109 and 366 nucleotides, respectively. Alignment of the MODV amino acid sequence with that of 20 other flaviviruses revealed several regions with high sequence similarity corresponding to functionally important domains (e.g., the serine protease/helicase/NTPase of NS3 and the methyltransferase/RNA-dependent RNA polymerase of NS5) and conserved sites for proteolytic cleavage by viral and cellular proteases. Phylogenetic analysis of the entire coding region confirmed the classification of MODV within the flaviviruses with no known vector, which is in agreement with previous findings based on partial NS5 sequences. A detailed comparative analysis of the putative folding patterns of the 5'- and 3'-UTR of MODV and of the tick- and mosquito-borne viruses was carried out. Structural elements in the 5'- and 3' UTR of MODV that are preserved among vector-borne flaviviruses were noted and so were structural elements distinguishing the MODV UTRs from mosquito-borne and tick-borne flaviviruses. Also the putative secondary structure of circularized MODV RNA is presented. 相似文献
82.
The Anti-HIV potency of cyclotriazadisulfonamide analogs is directly correlated with their ability to down-modulate the CD4 receptor 总被引:3,自引:0,他引:3
Vermeire K Bell TW Choi HJ Jin Q Samala MF Sodoma A De Clercq E Schols D 《Molecular pharmacology》2003,63(1):203-210
9-Benzyl-3-methylene-1,5-di-p-toluenesulfonyl-1,5,9-triazacyclododecane (CADA) has been identified as a novel antiviral lead compound with significant anti-human immunodeficiency virus and anti-human herpesvirus 7 activity. Surprisingly, this compound selectively decreased the expression of the CD4 glycoprotein, the primary receptor needed for the entry of both viruses. Herein, we describe the CD4 down-modulating and antiviral potencies of more than 25 CADA derivatives. Flow cytometric evaluation of cellular CD4 receptor expression in T cells demonstrated the specific CD4 down-modulating capacity of the CADA derivatives, with IC(50) values similar to those obtained in the antiviral assays. The close correlation observed between the CD4 down-regulating and anti-HIV potencies of the CADA derivatives further points to CD4 receptor down-modulation as the primary mode of antiviral action for this group of compounds. 相似文献
83.
Remoue F Diallo TO Angeli V Hervé M de Clercq D Schacht AM Charrier N Capron M Vercruysse J Ly A Capron A Riveau G 《Transactions of the Royal Society of Tropical Medicine and Hygiene》2003,97(3):361-364
The epidemiological coexistence of schistosomiasis and malaria is frequently observed in developing countries. Co-infection with malaria in children could influence the development of acquired immunity associated with the resistance or the pathology of schistosomiasis. In the present study, performed during May to June 1996 in Senegal, the humoral immune response to Schistosoma haematobium 28 kDa glutathione S-transferase (Sh28GST) vaccinal antigen and to soluble egg antigens (SEA) has been evaluated in individuals infected by S. haematobium. Specific immunoglobulin G3 (IgG3) and IgE responses were significantly higher in co-infected children with Plasmodium falciparum compared with children infected with S. haematobium only. In addition, circulating levels of interferon-gamma (IFN-gamma), interleukin-10 (IL-10), and soluble tumor necrosis factor receptor II (sTNF-RII), 3 parameters associated with schistosomiasis morbidity, were significantly increased in co-infected children. Taken together, this study indicated that malaria co-infection can both influence the acquired specific immune response to schistosome antigens and unbalance the regulation of inflammatory factors closely involved in schistosomiasis pathology. 相似文献
84.
Van Lancker P Abeloos JV De Clercq CA Mommaerts MY 《Acta anaesthesiologica Belgica》2003,54(3):223-226
The purpose of this study was to compare the efficacy of a mandibular nerve block to placebo, in patients undergoing mandibular osteotomy surgery, regarding opioid consumption and adverse opioid induced side effects. Forty healthy individuals with a mean age of 19.7 years participated in the study. All subjects received lidoca?n 2% + adrenaline 1/80,000 versus placebo for mandibular nerve block in a randomized double-blind manner. Opioid consumption and opioid related side effect such as postoperative nausea and vomiting (PONV), and respiratory depression were assessed. RESULTS: The placebo group received significantly more sufentanil during the surgical procedure than the lidoca?ngroup. There were no significant differences in adverse opioid induced side effects. In the postoperative phase there was no difference in additional pain intervention between the two groups. CONCLUSION: The mandibular block during mandibular osteotomy reduces intra-operative opioid consumption but does not alternate the opioid related side-effects in the postoperative phase. 相似文献
85.
Rao A Carbone A Chimirri A De Clercq E Monforte AM Monforte P Pannecouque C Zappalà M 《Il Farmaco; edizione pratica》2003,58(2):115-120
Several 1,3-thiazolidin-4-ones bearing a 2,6-dihalophenyl group at C-2 and a variously substituted phenyl ring at N-3 have been synthesized and tested as anti-HIV agents. The results of the in vitro tests showed that some of them proved to be effective inhibitors of HIV-1 replication. 相似文献
86.
Naimi E Zhou A Khalili P Wiebe LI Balzarini J De Clercq E Knaus EE 《Journal of medicinal chemistry》2003,46(6):995-1004
A group of 3'-O-nitro-2'-deoxyuridines, 3'-O-nitro-2'-deoxycytidines, and 5'-O-nitro-2'-deoxyuridines possessing a variety of substituents (H, Me, F, I) at the C-5 position were synthesized for evaluation as anticancer/antiviral agents that have the ability to concomitantly release cytotoxic nitric oxide (*NO). Although these compounds generally released a greater percent of *NO than the reference drug isosorbide dinitrate upon incubation in the presence of l-cysteine, or serum, their cytotoxicity (CC(50) = 10(-3) to 10(-6) M range) was comparable to 5-iodo-2'-deoxyuridine, but weaker than 5-fluoro-2'-deoxyuridine, against a variety of cancer cell lines. No differences in cytotoxicity against nontransfected (KBALB, 143B), and the corresponding transfected (KBALB-STK, 143B-LTK) cancer cell lines possessing the herpes simplex virus type 1 (HSV-1) thymidine kinase gene (TK(+)) were observed, indicating that expression of the viral TK enzyme did not provide a gene therapeutic effect. These nitrate esters were inactive antiviral agents except for 5-iodo-3'-O-nitro-2'-deoxyuridine that showed modest activity against HSV-1, HSV-2, and vaccinia virus. 相似文献
87.
Synthesis and biological evaluation of 5-substituted derivatives of the potent antiherpes agent (north)-methanocarbathymine 总被引:1,自引:0,他引:1
Russ P Schelling P Scapozza L Folkers G Clercq ED Marquez VE 《Journal of medicinal chemistry》2003,46(23):5045-5054
The conformationally locked nucleoside, (north)-methanocarbathymine (1a), is a potent and selective anti-herpes agent effective against herpes simplex type 1 (HSV1) and type 2 (HSV2) viruses. Hereby, we report on the synthesis and biological evaluation of a small set of 5-substituted pyrimidine nucleosides belonging to the same class of bicyclo[3.1.0]hexane nucleosides. Both the 5-bromovinyl (4) and the 5-bromo analogue (3) appeared to be exclusive substrates of HSV1 thymidine kinase (TK), contrasting with the 5-iodo analogue (2), which was significantly phosphorylated by the human cytosolic TK. The binding affinity constant and catalytic turnover for HSV1 TK were measured to assess the influence of the substitution on these parameters. In the plaque reduction and cytotoxicity assays, the 5-bromo analogue (3) showed good activity against HSV1 and HSV2 with less general toxicity than 1a. Against varicella-zoster virus (VZV), the north-locked 5-bromovinyl analogue (4) proved to be as potent as its conformationally unlocked 2'-deoxyriboside equivalent BVDU. The three compounds were also tested in vitro as prodrugs used in a gene therapy context on three osteosarcoma cell lines, either deficient in TK (TK(-)), nontransduced, or stably transduced with HSV1 TK. The 5-iodo compound (2, CC(50) 25 +/- 7 microM) was more efficient than ganciclovir (GCV, CC(50) 75 +/- 35 microM) in inhibiting growth of HSV1-TK transfected cells and less inhibitory than GCV toward TK(-) cells, whereas compound 3 inhibited transfected and nontransfected cell lines in a relatively similar dose-dependent manner. 相似文献
88.
Recently, studies have shown the benefits of using clinical guidelines in the practice of medicine. Computer-based clinical guidelines are increasingly applied in diverse areas such as policy development, utilization management, education, conduct of clinical trials, and workflow facilitation. This paper discusses some of the representations suggested in literature, discusses their weak and strong points, and demonstrates and discusses a new approach that extends earlier developed formalisms by combining primitives, ontologies and the use of problem-solving methods (PSMs). The approach is supported by a framework that facilitates the entire guideline authoring process. The paper demonstrates this framework and presents examples of guidelines, PSMs and systems that were developed by means of this approach. The overall goal of this approach is to improve the acceptance of shareable guidelines and decision support systems in daily care by facilitating the guideline acquisition and execution phases. 相似文献
89.
Neyt L Deryckere F Abeloos J De Clercq C Mommaerts M 《Revue belge de médecine dentaire》2001,56(1):9-14
This article describes the treatment of a boy with Class II deep bite and hypoplasia of the alveolar process due to agenesis of the canines and premolars. At first, the occlusion has been adjusted by advancement of the mandible and opening of the bite after bilateral sagittal split osteotomy. Later, under local anaesthesia, a segmental osteotomy of the hypoplastic alveolar process has been performed. Distraction of the hypoplastic alveolar process has been achieved by orthodontic traction on the residual dentition in the segments. After sufficient augmentation of the alveolar process, 6 implants for two bridges have been placed. 相似文献
90.
Zoidis G Kolocouris N Foscolos GB Kolocouris A Fytas G Karayannis P Padalko E Neyts J De Clercq E 《Antiviral chemistry & chemotherapy》2003,14(3):153-164
There is a lack of information in the medical chemistry literature concerning the anti-influenza A activity of the drug rimantadine's 2-isomer (2-rimantadine). We now present results showing that, although 2-adamantanamine (2-amantadine) 3 is only moderately active, some 2-rimantadine analogues are effective anti-influenza A virus agents in vitro. The 2-rimantadine analogues and their spirocyclobutane and spirocyclopentane congeners were synthesized through interesting routes. The 2-rimantadine analogues were 2-4 times more potent than rimantadine 2 against influenza virus A H2N2 strain; their spirocyclobutane congeners proved equally active to rimantadine 2. Two compounds exhibited a similar activity and one of the compounds was was fourfold more potent than rimantadine 2 against H3N2 strain. 相似文献