全文获取类型
收费全文 | 1042篇 |
免费 | 78篇 |
国内免费 | 8篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 18篇 |
妇产科学 | 4篇 |
基础医学 | 152篇 |
口腔科学 | 14篇 |
临床医学 | 125篇 |
内科学 | 186篇 |
皮肤病学 | 11篇 |
神经病学 | 87篇 |
特种医学 | 112篇 |
外科学 | 215篇 |
综合类 | 7篇 |
预防医学 | 38篇 |
眼科学 | 6篇 |
药学 | 89篇 |
中国医学 | 22篇 |
肿瘤学 | 38篇 |
出版年
2023年 | 4篇 |
2022年 | 6篇 |
2021年 | 23篇 |
2020年 | 14篇 |
2019年 | 23篇 |
2018年 | 30篇 |
2017年 | 15篇 |
2016年 | 15篇 |
2015年 | 32篇 |
2014年 | 36篇 |
2013年 | 53篇 |
2012年 | 98篇 |
2011年 | 89篇 |
2010年 | 54篇 |
2009年 | 53篇 |
2008年 | 82篇 |
2007年 | 79篇 |
2006年 | 84篇 |
2005年 | 80篇 |
2004年 | 65篇 |
2003年 | 51篇 |
2002年 | 44篇 |
2001年 | 6篇 |
2000年 | 9篇 |
1999年 | 4篇 |
1998年 | 14篇 |
1997年 | 9篇 |
1996年 | 11篇 |
1995年 | 4篇 |
1994年 | 6篇 |
1993年 | 4篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1983年 | 1篇 |
1981年 | 2篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1973年 | 1篇 |
1970年 | 1篇 |
1969年 | 2篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
1964年 | 2篇 |
1963年 | 1篇 |
排序方式: 共有1128条查询结果,搜索用时 703 毫秒
61.
Oertli D Marti WR Zajac P Noppen C Kocher T Padovan E Adamina M Schumacher R Harder F Heberer M Spagnoli GC 《Human gene therapy》2002,13(4):569-575
A specific cellular immune response directed against a panel of three defined tumor-associated antigen (TAA) epitopes was induced in metastatic melanoma patients by a prime-boost strategy taking advantage of an innovative recombinant vaccinia virus as evaluated by quantitative assessment of cytotoxic T lymphocytes (CTLs) with corresponding specificity. The immunization protocol consisted of the administration of psoralen-UV-treated and replication-incompetent recombinant vaccinia virus encoding the three immunodominant HLA-A*0201-restricted epitopes Melan-A(27-35), gp100(280-288), and tyrosinase(1-9) together with two costimulatory molecules, B7.1 and B7.2, in the context of systemic granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment. Boosts were subsequently applied with corresponding synthetic nonapeptides and GM-CSF. Specific CTL induction was assessed by tetramer staining and CTL precursor (CTLp) frequency evaluation. Within 12 days of injection of the recombinant vector, cytotoxic T cell responses specific for engineered epitopes were detectable in three of three patients. During the vaccination treatment, antigen-specific CTLp frequencies exceeding 1:10,000 peripheral CD8(+) T cells could be observed. Tetramer staining also revealed significant increases in specific CD8(+) T cell numbers. We conclude that active specific antitumor vaccination can raise a concurrent and specific cellular immune response against a panel of molecularly defined antigens, thereby increasing the chance of an immune hit against neoplastic cells with heterogeneous antigen expression. Data from this study emphasize the potency of a recombinant vaccinia virus vector encoding multiple minigenes and costimulatory molecules in the context of exogenously administered GM-CSF. Clinical effectiveness of this immunologically active protocol should therefore be explored in appropriately selected groups of patients. 相似文献
62.
BACKGROUND: To investigate the vasoactive effect of bimatoprost (Lumigan), a new topical ocular hypotensive agent, in isolated porcine ciliary arteries. MATERIAL AND METHODS: Arteries were placed in a myograph system to measure isometric forces. Quiescent vessels as well as vessels pre-contracted with either 10 nM endothelin-1 or 100 mM potassium chloride (KCl) were exposed, in a cumulative manner, to increasing concentrations (0.1 nM - 0.1 mM) of bimatoprost (dissolved in ethanol). In quiescent vessels, results were expressed in percent of 100 mM KCl-induced contraction. In endothelin-1-pre-contracted vessels, results were expressed in percent of the maximal contraction induced by endothelin-1. In KCl-pre-contracted vessels, results were expressed in percent of the plateau contraction reached 30 minutes after 100 mM KCl application. RESULTS: Bimatoprost induced a significant (p < 0.05 - 0.001) vasoconstriction at concentrations equal to or higher than 0.1 micro M in quiescent vessels (0.1 mM: 73 +/- 12 %). In KCl-pre-contracted vessels, at concentrations higher than 1 micro M, bimatoprost induced significant (p < 0.05 - 0.01) contractions (0.1 mM: 67 +/- 17 %). In endothelin-1-pre-contracted vessels, bimatoprost also induced significant (p < 0.05 - 0.001) contractions at concentrations above 10 micro M (0.1 mM: 17 +/- 8 %). CONCLUSIONS: The present study indicates that bimatoprost appears to have, in vitro, some vasoactive properties in porcine ciliary arteries. The question whether Lumigan has an influence on ocular blood flow needs to be further investigated. 相似文献
63.
Several novel derivatives bearing the 7-trifluoromethyl-4-(4-substituted anilino)-quinoline skeleton were synthesized and evaluated for their in vitro activity against the blood streaming form of the parasites Trypanosoma brucei rhodesiense, the trypomastigotes of Trypanosoma cruzi cultured in rat skeletal myoblasts, the amastigotes form of Leishmania donovani, Plasmodium falciparum (K1 strain) infected erythrocyte suspension, as well as their toxicity towards rat skeletal L-6 cells. In addition, three of the synthesized compounds were tested for their in vitro antitumor activity towards 60 human tumor cell lines by the National Cancer Institute (NCI). Compound 1-(4-[[7-(trifluoromethyl)quinolin-4-yl]amino]phenyl)ethan-1-one thiosemicarbazone 23 exhibited potential activity against T. b. rhodesiense, T. cruzi and P. falciparum with IC50's of 0.278, 0.85 and 0.417 microgram/ml, respectively. These values are even more valuable since this compound was clearly non-toxic (cytotoxicity IC50 > 90 micrograms/ml), leading to in vitro therapeutic indices of > 323, > 106 and > 216, respectively. Meanwhile, compound N-[4-[5-(4-chlorophenyl)-4,5-dihydroisoxazol-3-yl]phenyl]-7-(trifluoromethyl) quinolin-4-amine 21 showed broad spectrum antitumor activity with full panel median growth inhibition GI50 (MG-MID) of 1.95 mumol and total growth inhibition TGI (MG-MID) of 6.87 mumol, respectively. Compound 23 represents a very good prospective as a lead compound able to combat three tropical diseases at a time. However, the pattern for the antitumor activity did not parallel any of the antiparasitic ones, indicating that non-common mechanisms of action may exist among these activities. 相似文献
64.
Schmidt S Lepori D Meuwly JY Duvoisin B Meuli R Michetti P Felley C Schnyder P van Melle G Denys A 《European radiology》2003,13(6):1303-1311
Our objective was a prospective comparison of MR enteroclysis (MRE) with multidetector spiral-CT enteroclysis (MSCTE). Fifty
patients with various suspected small bowel diseases were investigated by MSCTE and MRE. The MSCTE was performed using slices
of 2.5 mm, immediately followed by MRE, obtaining T1- and T2-weighted sequences, including gadolinium-enhanced acquisition
with fat saturation. Three radiologists independently evaluated MSCTE and MRE searching for 12 pathological signs. Interobserver
agreement was calculated. Sensitivities and specificities resulted from comparison with pathological results (n=29) and patient's clinical evolution (n=21). Most pathological signs, such as bowel wall thickening (BWT), bowel wall enhancement (BWE) and lymphadenopathy (ADP),
showed better interobserver agreement on MSCTE than on MRE (BWT: 0.65 vs 0.48; BWE: 0.51 vs 0.37; ADP: 0.52 vs 0.15). Sensitivity
of MSCTE was higher than that of MRE in detecting BWT (88.9 vs 60%), BWE (78.6 vs 55.5%) and ADP (63.8 vs 14.3%). Wilcoxon
signed-rank test revealed significantly better sensitivity of MSCTE than that of MRE for each observer (p=0.028, p=0.046, p=0.028, respectively). Taking the given study design into account, MSCTE provides better sensitivity in detecting lesions
of the small bowel than MRE, with higher interobserver agreement.
Electronic Publication 相似文献
65.
Bringmann G Dreyer M Faber JH Dalsgaard PW Staerk D Jaroszewski JW Ndangalasi H Mbago F Brun R Reichert M Maksimenka K Christensen SB 《Journal of natural products》2003,66(9):1159-1165
The first phytochemical investigation of the recently discovered East African liana Ancistrocladus tanzaniensis is described, resulting in the isolation and structural elucidation of two new naphthylisoquinoline alkaloids, ancistrotanzanines A (5) and B (6), and the known compound ancistrotectoriline A (7). Ancistrotazanine A (5) represents a hitherto unprecedented 5,3'-coupling type between the naphthalene and isoquinoline portions, while 6 and 7 are 5,8'-coupled. The structures of the compounds were determined by spectroscopic, chemical, and chiroptical methods. Compounds 5 and 6 showed good activities against the pathogens of leishmaniasis and Chagas' disease, Leishmania donovani and Trypanosoma cruzi, while 5-7 displayed moderately potent antiplasmodial activities against Plasmodium falciparum parasites. 相似文献
66.
67.
68.
Reto A. Schwendener Heinz H. Fiebig Martin R. Berger Dietmar P. Berger 《Cancer chemotherapy and pharmacology》1991,27(6):429-439
Summary Mitoxantrone (MTO) was incorporated into small unilamellar liposomes by formation of a complex between the anticancer drug and negatively charged lipids. The complex was formed at a 2:1 molar ratio between the lipids and MTO, with phosphatidic acid (PA) being the strongest complex-forming lipid. Weaker complexes and lower incorporation rates of MTO resulted when liposomes containing dicetylphosphate, phosphatidyl inositol, phosphatidyl serine, phosphatidyl glycerol, oleic acid, and tridecylphosphate were used. Thus, all further experiments were performed with PA-MTO liposomes that contained 0.1–3 mg MTO/ml and had mean vesicle sizes of 40–150 nm, depending on the drug concentration and the method of liposome preparation. In vitro incubations of free and liposomal MTO with human plasma showed that the drug is slowly transferred from the liposome membranes to the plasma proteins. For liposomal MTO a transfer rate of 48% was determined, whereas 75.8% of free MTO was bound to the plasma proteins. The organ distribution of the two preparations in mice showed that higher and longer-lasting concentrations of liposomal MTO were found in the liver and spleen. The terminal elimination halflives in the liver were 77 h for liposomal MTO and 14.4 h for free MTO. In the blood, slightly higher concentrations were detected for liposomal MTO, which also had slower biphasic elimination kinetics as compared with the free drug. Drug distribution in the heart was not significantly different from that in the kidneys. The LD25 of PA-MTO liposomes in mice was 19.6 mg/kg and that of free MTO was 7.7 mg/kg. The antitumor effects of PA-MTO liposomes were evaluated in murine L 1210 leukemia, in various xenografted human tumors, and in methylnitrosourea-induced rat mammary carcinoma. Generally, the liposomal application form was more effective and less toxic than the free drug. The cytostatic effects were dependent on the tumor model, the application schedule, and the drug concentration. At doses that were toxic when free MTO was used, the liposomal preparation produced strong antitumor effects in some cases. In summary, the incorporation of MTO into liposomes changes the drug's plasmabinding properties, alters its organ distribution, reduces its acute toxicity, and increases its cytostatic efficiency in various tumor models. The liposomal PA-MTO complex represents a new application form of MTO that has advantageous properties.This research was supported in part by the Krebsliga of the Kanton Zürich and by Lederle Arzneimittel, Wolfratshausen, Federal Republic of Germany 相似文献
69.
70.
Nagamune K Acosta-Serrano A Uemura H Brun R Kunz-Renggli C Maeda Y Ferguson MA Kinoshita T 《The Journal of experimental medicine》2004,199(10):1445-1450
The African trypanosome Trypanosoma brucei, which causes sleeping sickness in humans and Nagana disease in livestock, is spread via blood-sucking Tsetse flies. In the fly's intestine, the trypanosomes survive digestive and trypanocidal environments, proliferate, and translocate into the salivary gland, where they become infectious to the next mammalian host. Here, we show that for successful survival in Tsetse flies, the trypanosomes use trans-sialidase to transfer sialic acids that they cannot synthesize from host's glycoconjugates to the glycosylphosphatidylinositols (GPIs), which are abundantly expressed on their surface. Trypanosomes lacking sialic acids due to a defective generation of GPI-anchored trans-sialidase could not survive in the intestine, but regained the ability to survive when sialylated by means of soluble trans-sialidase. Thus, surface sialic acids appear to protect the parasites from the digestive and trypanocidal environments in the midgut of Tsetse flies. 相似文献