全文获取类型
收费全文 | 284篇 |
免费 | 19篇 |
国内免费 | 2篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 18篇 |
妇产科学 | 2篇 |
基础医学 | 17篇 |
口腔科学 | 1篇 |
临床医学 | 16篇 |
内科学 | 26篇 |
皮肤病学 | 2篇 |
神经病学 | 26篇 |
特种医学 | 1篇 |
外科学 | 14篇 |
综合类 | 23篇 |
预防医学 | 5篇 |
眼科学 | 5篇 |
药学 | 49篇 |
中国医学 | 7篇 |
肿瘤学 | 88篇 |
出版年
2023年 | 3篇 |
2022年 | 4篇 |
2021年 | 5篇 |
2020年 | 5篇 |
2019年 | 3篇 |
2018年 | 5篇 |
2017年 | 5篇 |
2016年 | 7篇 |
2015年 | 7篇 |
2014年 | 12篇 |
2013年 | 8篇 |
2012年 | 15篇 |
2011年 | 16篇 |
2010年 | 12篇 |
2009年 | 9篇 |
2008年 | 22篇 |
2007年 | 7篇 |
2006年 | 20篇 |
2005年 | 11篇 |
2004年 | 10篇 |
2003年 | 7篇 |
2002年 | 11篇 |
2001年 | 11篇 |
2000年 | 4篇 |
1999年 | 7篇 |
1998年 | 13篇 |
1997年 | 5篇 |
1996年 | 5篇 |
1995年 | 7篇 |
1994年 | 10篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1991年 | 4篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1982年 | 5篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1972年 | 1篇 |
排序方式: 共有305条查询结果,搜索用时 16 毫秒
121.
Edwin Oto Jan Vaage Yolanda Quinn Mary Newman Charles Engbers P. Uster G. Zhu 《Cancer chemotherapy and pharmacology》1996,39(1-2):138-142
Poly(ethylene glycol) (PEG)-derivatized liposome vehicles improve antitumor effectiveness of entrapped anthracyclines and
vinca alkaloids. However, the plasma clearance of entrapped vincristine is substantially faster than the lipid phase or other
entrapped aqueous markers, suggesting leakage out of the liposome during transit in the blood compartment. We tested the effect
of altering the drug’s in vivo leakage rate on pharmacokinetics, toxicity, and antitumor activity of entrapped drug in rodent
models. Suramin, heparin, and dextran sulfate were tested for their ability to produce a precipitable complex in vitro. PEG-derivatized
liposomes were prepared with the complexing agent inside, and vincristine was driven inside using an ammonium gradient. The
resulting preparations were found to have plasma distribution half-lives significantly longer than the formulation without
a complex-forming agent. There was no increase in acute lethality, and in the case of the suramin-vincristine complex, the
acute lethality was significantly reduced at the highest does level. Anti-tumor activity against the mouse mammary carcinoma
MC2 was tested in a multiple-dose study. Free vincristine did not affect the tumor growth rate significantly, but at the same
dose level all PEG-coated liposome formulations inhibited tumor growth markedly. The suramin containing formulation was as
effective as the formulation lacking polyanion, but the heparin and dextran sulfate containing formulations were less effective.
Thus, compounds which form insoluble complexes with vincristine alter in vivo plasma distribution phase pharmacokinetics without
increasing acute lethality, but without a corresponding increase in anti-tumor activity.
Received: 28 August 1995/Accepted: 21 February 1996 相似文献
122.
Summary In order to investigate the influence of a cell-cycle specific agent on the cytokinetic behavior of a leukemic cell population in vivo, labeling studies with tritiated thymidine (3HTDR) followed by administration of vincristine (VCR) were performed on thymic cells of advanced AKR leukemic mice and evaluated utilizing a combined autoradiographic-Feulgen-microspectrophotometric technique. Twelve hours after a single drug injection the stathmokinetic effect of VCR was observed as reflected by an accumulation of cells in the S/G2-M phase of the mitotic cycle. Within 28 h this effect was no longer evident, but the significant increase in % unlabeled S/G2-M cells strongly suggested an influx of previously non-proliferating cells into the proliferating compartment (recruitment).Supported by the Deutsche Forschungsgemeinschaft (Forschergruppe Leukämie- und Immuntherapie)Presented in part at the 5th Meeting of the International Society of Haematology, European and African Division, Hamburg, August 26–31, 1979 相似文献
123.
Actinomycin-D (Act-D) and vincristine (VCR) are cytotoxic agents commonly used in the treatment of pediatric cancers. To date,
there are few published methods on quantifying Act-D or VCR and no published methods on quantifying the two drugs together.
We present a methodology for the simultaneous quantification of Act-D and VCR in human plasma using liquid chromatography-tandem
mass spectrometry (LC/MS/MS) detection. Following solid phase extraction, plasma samples were separated and analyzed using
electrospray ionization (ESI). The lower limit of quantitation (LLOQ) for both Act-D and VCR was 0.5 ng/ml. The analytical
accuracy for detection of both Act-D and VCR was ≥ 90%. The analytical precision, as estimated by the coefficient of variation
was ≤ 6% for Act-D and ≤ 11% for VCR. Given the prevalence of the use of the two drugs as combination therapy in a variety
of pediatric oncological indications, the small sample volume requirements and the assay sensitivity, this methodology is
expected to support several ongoing and future pediatric trials. 相似文献
124.
125.
The effect of microtubular-poisons, such as colchicine and vincristine, on frog skin permeability has been investigated. Three-hour treatment with the drugs has no effect on nonelectrolyte basal transepithelial permeability, but completely supresses the effect of ADH. Colchicine and vincristine, in addition, affect both basal sodium transport and the rise in short circuit current induced by vasopressin.The inhibition produced by microtubular-poisons disappears, however, when hydrocortisone, a glucocorticoid known to preserve junctional communications is used.Together with the results previously obtained with isolated epithelial cells (Svelto et al. 1979), these findings provide further support for our hypothesis that the microtubularmicrofilament-system, is involved in cell-to-cell exchange. 相似文献
126.
目的:观察体外应用去甲二氢愈创木酸(NDGA)、氨甲喋呤(MTX)、长春新碱(VCR)3种药物单用或合用对人恶性胶质瘤细胞株SHG-44细胞的作用,并探讨其作用的可能机制。方法:用MTT法检测药物作用效应,用免疫组化染色法检测细胞CyclinD1基因的蛋白表达情况。结果:①3种药物单用及两药合用时随着药物浓度的增加其抗肿瘤效应也增加,且两药合用药物的效应增强;②先给NDGA24h后再给MTX或VCR,与同时给药对该细胞的抗肿瘤效应差异无显著性(P>0.05),而先给MTX或VCR24h后再给NDGA,与同时给药对细胞的抗肿瘤效应差异有显著性(P<0.05);③免疫组化染色结果显示,与对照组相比,NDGA处理后该细胞Cyclin D1基因的蛋白表达明显降低。结论:NDGA与MTX或VCR间有 协同作用,且这种作用可能与NDGA降低细胞cyclin D1基因的蛋白表达有关。 相似文献
127.
目的 制备合适尺寸的负载药物的纳米制剂,通过表面修饰,获取一种具有缓控释性的脑组织药物递送系统。方法 琥珀酸胆甾醇酯(CHS)与普鲁兰多糖经酯化反应形成疏水改性普鲁兰多糖(CHP)。CHP再通过透析法负载长春新碱(VCR)及通过乳化作用对聚山梨酯80(PS-80)进行表面修饰,得到VCR-CHP-PS纳米粒子。利用傅立叶红外光谱仪(FTIR)、核磁共振氢谱仪(1H-NMR)对聚合物进行表征,动态光散射仪表征纳米粒子的粒径及电位。透射电镜观测CHP形态,并用等温滴定量热法测定载药纳米粒子VCR-CHP对PS-80的吸附特性。结果 FTIR和1H-NMR证明CHS和CHP已成功合成。VCR-CHP-PS纳米粒子的平均粒径为414.2 nm,平均PDI为0.325,平均Zeta电位约为-19.5 mV。PS-80在CHP纳米粒子上的覆盖率为(149±43.5)%。VCR-CHP纳米粒子中VCR的载药量约为5.36%,包封率约为61.14%,72 h释放量约为61.43%。结论 疏水改性普鲁兰多糖纳米制剂具有较好的载药量和包封率及一定的缓释功能,有望成为脑靶向纳米药物载体。 相似文献
128.
Rosiglitazone (ROSI), an oral antidiabetic agent, has been reported the anti-cancer properties recent years. In this paper, the potency of ROSI as a synergistic drug for vincristine (VCR) on resistant oral cancer cells was investigated. We found that ROSI potently enhanced the susceptibility of KB cells or KB/V cells to VCR in a dose manner and the synergy in KB/V cells was much more prominent than that in KB cells. The synergistic anti-proliferative effect of ROSI and VCR was associated with inhibition on tubulin polymerization, cell cycle arrest in G2/M phase and cell apoptosis induction, but has no effect on drug efflux-protein P-gp and was independent with PPARγ. The combination treatment of ROSI and VCR could regulate the PTEN/PI3K/AKT survival pathway with an upregulation of PTEN and down-regulation of p-AKT. The effect of G2/M phase arrest was associated with the upregulation of cyclin B1 and downregulation of p-cdc2. The apoptosis induction of ROSI and VCR was partly due to an upregulation of cleaved PARP and downregulation of Bcl-2/Bax ratio. In addition, combination treatment of ROSI and VCR had also shown anti-angiogenic effect by suppressing the migration and blocking the capillary tube formation of HUVECs. More importantly, this combination treatment induced an acceptably weak cytotoxicity in human normal HL-7702 cells, GES-1 cells and HUVECs. Taken together, ROSI may be used as a potential compound for combinatorial therapy or as a complement to VCR for treatment on oral cancer, especially on that have acquired resistance to VCR therapy. 相似文献
129.
目的了解长春新碱(VCR)、甲基强的松龙(mPSL)诱导原代急性淋巴细胞白血病(ALL)细胞凋亡及其规律。方法应用细胞形态学检查,二苯胺法DNA片断化定量及DNA凝胶电泳方法分析检测。结果发现ALL细胞体外孵育24h,空白组DNA片断率为(169±4.6)%,加VCR1μM组和mPSL1μM组DNA片断率分别为(50.7±9.7)%(P<0.05,n=12)和(37.5±11.7)%(P<0.05,n=12)。两种药物诱导DNA片断化均呈剂量和时间依赖性。光镜下检查见细胞核固缩、碎裂,凋亡小体形成。DNA电泳显示典型的DNAladder,其亮度随剂量增加或时间延长而增强。结论VCR和mPSL诱导ALL细胞出现凋亡,可能是其抗白血病的机制之一。 相似文献
130.
C. E. M. Gidding G. J. Meeuwsen-de Boer P. Koopmans D. R. A. Uges W. A. Kamps S. S. N. de Graaf 《Cancer chemotherapy and pharmacology》1999,44(3):203-209
Purpose: We studied vincristine disposition after 169 weekly i.v. bolus injections in 32 children with acute lymphoblastic leukemia,
non-Hodgkin lymphoma, or Wilms' tumor. The aim of the study was to determine intrapatient and interpatient variability in
vincristine disposition and demographic, clinical, and biochemical characteristics influencing this variability. Methods: Vincristine plasma concentrations were measured by a high-performance liquid chromatography assay with electrochemical detection.
A limited sampling strategy was used based on a bayesian parameter estimation algorithm that is part of the ADAPT II software
package. A two-compartment, first-order model was fitted to the data, and pharmacokinetic parameters were calculated from
the model using the ADAPT II software. For statistical analysis, analysis of variance (ANOVA), t test, simple and multiple regression analysis, and non-parametric or robust equivalents were used. Results: Results showed a large intrapatient and interpatient variability in distribution half-life, elimination half-life, total
body clearance, apparent volume of distribution at steady state, and area under the concentration–time curve. Intrapatient
variability was significantly smaller than interpatient variability for all these parameters except distribution half-life.
The diagnosis or treatment protocol turned out to be the most predictive characteristic; leukemia and non-Hodgkin lymphoma
patients had a significantly higher total body clearance than Wilms' tumor patients. Conclusions: We conclude that both intrapatient and interpatient variability in vincristine pharmacokinetics is large in pediatric cancer
patients and that variability, although significantly influenced by diagnosis, largely remains unpredictable.
Received: 11 September 1998 / Accepted: 5 February 1999 相似文献