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51.
Conny J. van der Laken Otto C. Boerman Wim J. G. Oyen Marjo T. P. van de Ven Jos W. M. van der Meer Frans H. M. Corstens 《European journal of nuclear medicine and molecular imaging》1998,25(4):347-352
Previous studies have reported the favourable characteristics of chemotactic peptides and interleukins for imaging of infection
and inflammation. In the present study, the potential of two species of interleukin 1 (IL-1), IL-1α and IL-1β, the IL-1 receptor
antagonist (IL-1ra) and the synthetic chemotactic peptide N-formyl-methionyl-leucyl-phenylalanyl-lysine (fMLFK) were directly compared in a rabbit model of infection. IL-1α, IL-1β,
IL-1ra and fMLFK were labelled with iodine-123 according to the Bolton-Hunter method. Twenty-four hours after induction of
Escherichia coli abscesses in the left thigh muscle, rabbits were injected intravenously with 0.5 mCi of 123I-labelled agent. Gamma camera images were obtained at 5 min and 1, 4, 8 and 20 h p.i. Biodistribution was determined at 20 h
p.i. Although all agents rapidly cleared from the blood, at 20 h p.i. blood levels and the levels in most organs of 123I-fMLFK were significantly lower than those of the other three agents (P<0.05). The abscesses were clearly visualized with all agents from 4 h p.i. onwards. After 1 h p.i., the abscess uptake of
123I-IL-1β was significantly higher than that of the other agents (P<0.05), with the highest uptake observed at 8 h p.i. (1.3%±0.3%). After 20 h p.i., the highest abscess-to-contralateral muscle
ratios were obtained with 123I-IL-1β, i.e. 39.0±11.5 vs 18.7±5.4, 18.1±2.3 and 29.9±7.0 for 123I-IL-1α, 123I-IL-1ra and 123I-fMLFK, respectively. In conclusion, all agents localized in the infectious focus. The potential of radiolabelled IL-1β for
imaging of infection was better than that of the other agents: higher absolute uptake in the infection and higher abscess-to-contralateral
muscle ratios were obtained. The observation of localization of radiolabelled IL-1ra in infection was important since this
protein can be administered to humans without any side-effects.
Received 11 October and in revised form 27 December 1997 相似文献
52.
单克隆抗体—表阿霉素免疫偶合物的制备和体外活性 总被引:14,自引:0,他引:14
用双功能试剂己二酰肼制备腙键连接的聚谷氨酸—表阿霉素,通过控制交联条件,所得产物克服了大分子自身交联的缺点,交联率较高。聚谷氨酸的载药量与分子量呈正比,平均每8~11个谷氨酸单体连接1分子表阿霉素。分子量为14300的聚谷氨酸做载体其载药量为1:11,与单抗交联所得的偶合物McAb:PGA:PAR为1:2:22。偶合物较好地保留了抗体活性,体外细胞毒性较游离药物略有下降,但表现出单抗介导的靶细胞选择性杀伤作用。本研究用腙键交联法成功地制备了药/抗比高且体外有效的免疫偶合物,为进一步制备细胞靶向的肿瘤化疗制剂奠定了基础。 相似文献
53.
54.
Julli?tte E M van Eerd Wim J G Oyen Thomas D Harris Huub J J M Rennen D Scott Edwards Shuang Liu Charles E Ellars Frans H M Corstens Otto C Boerman 《Journal of nuclear medicine》2003,44(7):1087-1091
Several radiolabeled chemotactic peptides have been tested for their suitability to show infection and inflammation. Leukotriene B(4) (LTB(4)) receptor-binding ligands could be useful agents for revealing neutrophilic infiltrations because the LTB(4) receptor is abundantly expressed on neutrophils after an inflammatory stimulus. In this study, we investigated the in vivo and in vitro characteristics of a new hydrophilic (111)In-labeled LTB(4) antagonist. METHODS: The LTB(4) antagonist DPC11870-11 was labeled with (111)In and intravenously injected into New Zealand White rabbits with Escherichia coli infection in the left thigh muscle. The pharmacokinetics and biodistribution were studied by serial scintigraphic imaging (0-24 h after injection) and by ex vivo counting of dissected tissues (6 and 24 h after injection). The receptor-mediated in vivo localization of the compound was investigated in 3 rabbits that received an excess of nonradioactive indium-labeled agent 2 min before the administration of the (111)In-labeled LTB(4) antagonist. RESULTS: In rabbits with intramuscular E. coli infection, the abscess was visualized as early as 2 h after injection. Accumulation in the abscess increased with time, resulting in excellent images at 6 h after injection. Blood clearance was rapid in the first hours after injection (alpha-half-life = 30 +/- 6 min, 85%; beta-half-life = 25.7 +/- 0.8 h, 15%). Abscess-to-background ratios, as derived from the region-of-interest analysis, increased to 34 +/- 7 at 24 h after injection. The images of both groups showed moderate uptake in the liver, spleen, kidneys, and bone marrow. No activity was seen in the bladder, indicating almost complete retention in the kidneys. The uptake in the abscess could be blocked completely by injection of an excess of nonradioactive agent, indicating a specific receptor-ligand interaction of the radiolabeled agent in the infected tissue. Biodistribution data showed that after saturation of the LTB(4) receptor, the abscess uptake, in percentage injected dose per gram, was significantly reduced (0.03 +/- 0.02 vs. 0.24 +/- 0.06, P = 0.008). CONCLUSION: The modified LTB(4) antagonist showed infectious foci rapidly after injection because of specific receptor-ligand interaction. Because of the high abscess-to-background ratios that were obtained and the fact that no accumulation of radioactivity was observed in the gastrointestinal tract, this compound has excellent characteristics for revealing infectious and inflammatory foci. 相似文献
55.
刺南蛇藤倍半萜的研究 总被引:1,自引:0,他引:1
从刺南蛇藤(Celastrus flagelaris Rupr.)种子油中分离到八个β-二氢沉香呋喃倍半萜,经红外、紫外、质谱及核磁共振谱确定它们的结构是1α-乙酰氧基-2α,9β-二肉桂酰氧基-β-二氢沉香呋喃(1),1α,6β,13-三乙酰氧基-9β-苯甲酰氧基-β-二氢沉香呋喃-(2),triptogelinG-1(3),1α,6β-二乙酰氧基-9β-苯甲酰氧基-β-二氢沉香呋喃(4),triptogelinF-2(5),1α,2α-二乙酰氧基-9β-肉桂酰氧基-β-二氢沉香呋喃(6),celaforlinB-3(7),1α,6β-二乙酰氧基-8α-肉桂酰氧基-9α-苯酰氧基-β-二氢沉香呋喃(8)。其中1是新化合物,命名为celastrine B。 相似文献
56.
Preferential localization of systemically administered radiolabeled interleukin 1alpha in experimental inflammation in mice by binding to the type II receptor. 总被引:1,自引:0,他引:1
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C J van der Laken O C Boerman W J Oyen M T van de Ven R Chizzonite F H Corstens J W van der Meer 《The Journal of clinical investigation》1997,100(12):2970-2976
Previously, we have shown that systemically administered radiolabeled interleukin 1alpha (IL-1alpha) accumulates preferentially in inflammatory foci in mice. Since inflammation is characterized by influx of leukocytes, which represent IL-1 receptor (IL-1R) positive cells, radiolabeled IL-1 may specifically localize in inflammation by binding to its receptors on infiltrated leukocytes. This hypothesis was tested in a series of studies in mice with acute focal inflammations. Evidence for specific IL-1-IL-1R interaction in induced inflammation was found: microscopic autoradiography revealed that 125I-IL-1alpha localized at the site of inflammatory cells with time; 125I-myoglobin, a similar-sized protein with no known interactions in vivo, was not retained in the inflammation. Furthermore, the uptake 125I-IL-1alpha in inflammatory tissue was significantly lower in neutropenic mice than in immunocompetent mice (0.05+/-0.004 vs. 0.65+/-0.06% ID/g at 48 h after injection, P < 0.0007). Moreover, the uptake of 125I-IL-1alpha at the inflammatory site could be blocked with the anti-IL-1R type II antibody 4E2. At 48 h after injection, the uptake with and without blocking the type II IL-1R was 0.13+/-0.01 and 0. 65+/-0.05% ID/g, respectively (P < 0.0001). These in vivo studies provide evidence that systemically administered radiolabeled IL-1alpha localizes in inflammatory tissue by specific receptor binding, predominantly by binding to the type II IL-1R. 相似文献
57.
58.
Pretargeted radioimmunotherapy of cancer: progress step by step. 总被引:14,自引:0,他引:14
Otto C Boerman Frank G van Schaijk Wim J G Oyen Frans H M Corstens 《Journal of nuclear medicine》2003,44(3):400-411
To enhance the therapeutic efficacy of radioimmunotherapy of cancer, several pretargeting strategies have been developed. In pretargeted radioimmunotherapy, the tumor is pretargeted with an antibody construct that has affinity for the tumor-associated antigen on the one hand and for a radiolabeled hapten on the other. The radiolabeled hapten is administered in a later phase, preferably after the antibody construct has cleared from the circulation. In pretargeted radioimmunotherapy, 2 main approaches can be distinguished: pretargeting strategies based on the avid interaction between streptavidin (SA) or avidin and biotin, and pretargeting strategies based on the use of bispecific antibodies. In pretargeting strategies based on biotin and SA or avidin, the use of a clearing agent that could remove the pretargeting construct from the circulation markedly improved the targeting of the radiolabeled biotin to the tumor. Thus, multistep injection schemes in which 3-5 different agents are subsequently injected were developed. In bispecific antibody-based pretargeting strategies, the use of bivalent haptens improved the efficacy of the tumor targeting, and a 2-step pretargeted radioimmunotherapy strategy is now being tested in cancer patients. Preclinical studies as well as studies on cancer patients have shown that these pretargeting strategies can result in higher radiation doses to the tumor than can directly radiolabeled antitumor antibodies. Here, the development and state of the art of the most effective approaches for pretargeted radioimmunotherapy are reviewed. 相似文献
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