全文获取类型
收费全文 | 400篇 |
免费 | 21篇 |
国内免费 | 17篇 |
专业分类
儿科学 | 4篇 |
妇产科学 | 1篇 |
基础医学 | 68篇 |
口腔科学 | 6篇 |
临床医学 | 40篇 |
内科学 | 59篇 |
皮肤病学 | 14篇 |
神经病学 | 52篇 |
特种医学 | 1篇 |
外科学 | 20篇 |
综合类 | 42篇 |
预防医学 | 2篇 |
眼科学 | 8篇 |
药学 | 86篇 |
中国医学 | 26篇 |
肿瘤学 | 9篇 |
出版年
2023年 | 8篇 |
2022年 | 7篇 |
2021年 | 10篇 |
2020年 | 12篇 |
2019年 | 4篇 |
2018年 | 9篇 |
2017年 | 11篇 |
2016年 | 7篇 |
2015年 | 5篇 |
2014年 | 17篇 |
2013年 | 32篇 |
2012年 | 9篇 |
2011年 | 23篇 |
2010年 | 6篇 |
2009年 | 10篇 |
2008年 | 10篇 |
2007年 | 8篇 |
2006年 | 14篇 |
2005年 | 14篇 |
2004年 | 13篇 |
2003年 | 15篇 |
2002年 | 9篇 |
2001年 | 11篇 |
2000年 | 5篇 |
1999年 | 7篇 |
1998年 | 10篇 |
1997年 | 11篇 |
1996年 | 9篇 |
1995年 | 13篇 |
1994年 | 7篇 |
1993年 | 7篇 |
1992年 | 4篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1989年 | 10篇 |
1988年 | 2篇 |
1987年 | 7篇 |
1986年 | 11篇 |
1985年 | 5篇 |
1984年 | 7篇 |
1983年 | 6篇 |
1982年 | 9篇 |
1981年 | 12篇 |
1980年 | 7篇 |
1979年 | 3篇 |
1978年 | 4篇 |
1976年 | 2篇 |
1975年 | 4篇 |
1974年 | 3篇 |
1973年 | 2篇 |
排序方式: 共有438条查询结果,搜索用时 15 毫秒
1.
Nishikawa S 《Anatomical science international / Japanese Association of Anatomists》2002,77(3):175-181
Apoptosis of ameloblasts were examined by the TdT-mediated dUTP-biotin nick end-labelling method and electron microscopy 8
h after injection of colchicine. The results showed that extensive apoptosis occurred in ameloblasts of secretion to maturation
zones. To determine the possible involvement of stimulators in ameloblast apoptosis, Fas, Fas ligand, tumor-necrosis-factor
α, and tumor-necrosis-factor receptor 1 were examined utilizing immunohistochemistry and Western blotting analysis. Only Fas
was consistently detected in the secretion, transition and maturation ameloblasts and overlying enamel organ epithelia. These
results suggest that ameloblasts could undergo apoptosis by colchicine and that one of the ameloblast apoptosis mediators
would be the Fas receptor. 相似文献
2.
Zamora-Perez A Zúñiga-González GM Gómez-Meda BC Ramos-Ibarra ML Batista-González CM Torres-Bugarín O 《Environmental and molecular mutagenesis》2004,44(5):436-440
The micronucleus (MN) assay can be used to detect the genotoxic effects of chemical agents in virtually any cell that divides frequently. Salamanders (Ambystoma sp.) are amphibians that can be easily maintained and bred in the laboratory and spontaneously shed their skin every 2.5-4 days. In this present study, we have evaluated the usefulness of this shed skin for the MN assay. We exposed salamanders to different concentrations of both the aneugen colchicine (COL) and the clastogen cyclophosphamide (CP) and we determined the frequency of micronucleated cells (MNCs) in their sheds. Fragments of shed skin were placed on clean slides, fixed, stained, observed with a light microscope, and the number of MNCs was counted. The MNC frequency was increased significantly by all doses of COL and CP tested, administered either as single or repeated exposures. The presence of MNCs in the shed skin and the speed of sloughing lead us to propose that the sheds of Ambystoma sp., or other amphibians that slough their skin, are suitable alternative models for detecting genotoxic exposures relevant to aquatic environments. 相似文献
3.
4.
5.
Ernest Hamel Andrei V. Blokhin Dale G. Nagle Hye-Dong Yoo William H. Gerwick 《Drug development research》1995,34(2):110-120
Curacin A is a newly isolated lipid natural product that binds in the colchicine site of tubulin and inhibits mitosis. We have examined its effects on tubulin polymerization, studied by turbidimetry, under three reaction conditions. In 1.0 M glutamate + 1.0 mM MgCl2, with a 37°C reaction temperature, we could find no concentration of curacin A that completely inhibited polymerization. A maximal inhibitory effect on turbidity development (about 50%) was observed with 5 m?M drug. Higher drug concentrations induced an abnormal polymerization reaction, which at 40 m?M differed little from the control reaction except for slightly delayed depolymerization in response to reducing the temperature to 0°C. In 0.8 M glutamate (no MgCl2), with a 30°C reaction temperature, complete inhibition did occur at 3–5 m?M drug, but higher drug concentrations again induced an abnormal polymerization reaction. With 40 m?M curacin A this reaction was also similar to the control reaction, except that cold-induced depolymerization was slightly enhanced relative to the control. When polymerization was induced by microtubule-associated proteins, maximal inhibition of turbidity development (about 70%) occurred with 2 m?M drug, with higher curacin A concentrations inducing abnormal polymerization reactions that reached about 60% of the control turbidity readings. Under all three reaction conditions the polymer induced by high concentrations of curacin A consisted of large aggregates of tightly coiled spiral fibers that had a 2–3 filament substructure. The implications of these findings with curacin A are discussed in terms of the use of tubulin polymerization assays as a screen for identifying new antimitotic drugs. © 1995 Wiley-Liss, Inc. 1 This article is a US Government work and, as such, is in the public domain in the United States of America. 相似文献
6.
7.
8.
《Expert review of anticancer therapy》2013,13(10):1433-1447
Microtubules and their component protein, tubulin, constitute a popular target for the treatment of cancer. Many drugs that are presently used in clinics or in clinical trials and drugs that show promise as anticancer drugs bind to tubulin and microtubules. There are three conventional binding sites on β-tubulin where many of these drugs bind. The binding properties, conformational changes upon binding, association constants and thermodynamic parameters for the drug–tubulin interaction on these three sites are discussed. The antiproliferative activities of these drugs and the possible correlation with the binding properties are also described. 相似文献
9.
《Renal failure》2013,35(9):899-903
The multidrug resistance gene-1 (MDR1, adenosine triphosphate-binding cassette transporter: ABCB1, P-glycoprotein) encodes membrane proteins that play a crucial role in protecting cells from xenobiotics, chemicals, and drugs. The TT genotype of 3435 codon in exon 26 of MDR1 gene causes overexpression of gene activity and effluxes many chemically diverse compounds across the plasma membrane. We studied the association between C3435T polymorphisms (single nucleotide polymorphism) of MDR1 gene and colchicine-resistant familial Mediterranean fever (FMF) patients. Total genomic DNA samples from 52 FMF patients of colchicine unresponsiveness were used for FMF (MEFV) and MDR1 genes profile analyses. Target genes were genotyped by multiplex PCR-based reverse-hybridization Strip Assay method. The preliminary current results showed increased T allele frequency (0.596) in colchicine unresponsiveness of FMF patients. The distributions of the CC, CT, and TT genotypes in colchicine nonresponder FMF patients were 17%, 46%, and 37%, respectively. Our results indicate that C3435T polymorphism in exon 26 of MDR1 gene is associated with colchicine resistance in nonresponder FMF patients during the common therapy protocol. 相似文献
10.
Yehuda Adler Yaron Finkelstein Abid Assali Josep Guindo Antoni Bayes-Genis Antony Bayes De Luna Asaad Khouri 《Clinical cardiology》1998,21(2):143-144
On the basis of our reported experience with colchicine for recurrent pericarditis, we administered colchicine to two patients with large pericardial effusions complicating idiopathic pericarditis. The first was a 26-year-old male who showed clinical deterioration following emergency pericardiocentesis and aspirin (3 g/day) for 10 days; the second was a 2-year-old girl who was unsuccessfully treated with aspirin (100 mg/kg/day) for 2 weeks, followed by corti-costeroids for 7 months. Administration of colchicine (1 mg/ day) instead of aspirin in the first case, and with a rapid tapering-off of the corticosteroids in the second case, led to complete regression of the pericardial effusion on echocardiography within 1 week and 1 month, respectively. Colchicine was discontinued after 1 month in the first patient and was continued for 6 months in the child. Neither has had a recurrence at 24 and 6 months of follow-up, respectively. No side effects of colchicine were observed. We conclude that colchicine may be effective in the treatment of large pericardial effusion when therapy with nonsteroidal anti-inflammatory drugs and/or corticosteroids fails. 相似文献