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91.
Folkes AJ Ahmadi K Alderton WK Alix S Baker SJ Box G Chuckowree IS Clarke PA Depledge P Eccles SA Friedman LS Hayes A Hancox TC Kugendradas A Lensun L Moore P Olivero AG Pang J Patel S Pergl-Wilson GH Raynaud FI Robson A Saghir N Salphati L Sohal S Ultsch MH Valenti M Wallweber HJ Wan NC Wiesmann C Workman P Zhyvoloup A Zvelebil MJ Shuttleworth SJ 《Journal of medicinal chemistry》2008,51(18):5522-5532
Phosphatidylinositol-3-kinase (PI3K) is an important target in cancer due to the deregulation of the PI3K/ Akt signaling pathway in a wide variety of tumors. A series of thieno[3,2-d]pyrimidine derivatives were prepared and evaluated as inhibitors of PI3 kinase p110alpha. The synthesis, biological activity, and further profiling of these compounds are described. This work resulted in the discovery of 17, GDC-0941, which is a potent, selective, orally bioavailable inhibitor of PI3K and is currently being evaluated in human clinical trials for the treatment of cancer. 相似文献
92.
93.
Sulaiman Ali Muhammad Subban Ravi Arumugam Thangamani 《Medicinal chemistry research》2016,25(5):994-1004
Novel N-substituted rhodanines 2a–g were synthesized by conventional and microwave-assisted methods and tested for their anticancer activity. Structure–activity relationship of the synthesized rhodanine 2a–g as antiproliferative agents was investigated. The results revealed that all the seven compounds showed potent antiproliferative activity in a concentration-dependent manner on leukemic cell line K562. Among the tested compounds, 2b was found to be more potent when compared by trypan blue and MTT assay. IC50 values of 2b using trypan blue and MTT assay were found to be 11.1 and 20.3 µg/ml, respectively. A dose-dependent increase in the LDH release was also observed upon treatment with 2a–g. Cell cycle analysis revealed that 2b affects DNA replication and leads to accumulation of cells in G 0 and decline of G 2/M, G 1 and S phases which indicates apoptosis. The selective cytotoxic activity against human chronic myelogenous cell line (K562), via apoptosis, suggests that compound 2b is a promising scaffold for the development of novel anticancer drug. 相似文献
94.
95.
Arumugam Somasundaram Ramadoss Karthikeyan Vadivel Velmurugan Balasubramanian Dhandapani Muthu Raja 《Journal of ethnopharmacology》2010
Aim of study
In view of the use of rhizomes of Kyllinga nemoralis L., against hepatopathy in ethnomedicine the present study was aimed at evaluating the hepatoprotective activity of the rhizomes of Kyllinga nemoralis against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats.Materials and methods
Hepatotoxicity was induced in male Wistar rats by carbon tetrachloride and olive oil (50%, v/v). i.p. ethanolic and petroleum ether extracts of Kyllinga nemoralis rhizomes were administered to the experimental rats (100 and 200 mg/kg, p.o. for seven days). The hepatoprotective effect of these extracts was evaluated by the assay of liver function biochemical parameters and histopathological studies of the liver compared with silymarin.Results
Both extracts showed significant hepatoprotection when compared to control, similar to standard silymarin. Histology of liver sections also revealed that the extracts protected liver from injury.Conclusions
The study identified a plant with potential hepatoprotective constituents which will be isolated and characterized in future. 相似文献96.
Eighteen patients aged 60-84 years with acute myeloid leukemia were treated with low-dose combination chemotherapy comprising cytarabine, etoposide, and mitozantrone or 6-thioguanine; seven of these patients had a pre-existing myelodysplastic syndrome. Nine patients achieved a complete remission, and five had a partial remission. The duration of survival in these 14 responding patients has ranged from 2+ to 19+ months. Myelotoxicity occurred regularly, with time to recovery (neutrophils ≥0.5 × 109/L, platelets ≥50 × 109/L) from nadir being 10-14 days in 12 of the 14 patients. This novel approach with an overall response rate of 78% appears to be a simple and effective form of therapy for elderly patients. Am. J. Hematol. 55:115-117, 1997. © 1997 Wiley-Liss, Inc. 相似文献
97.
Lauren Stevenson Marian Kelley Boris Gorovits Clare Kingsley Heather Myler Karolina Österlund Arumugam Muruganandam Yoshiyuki Minamide Mario Dominguez 《The AAPS journal》2014,16(1):83-88
The L2 Global Harmonization Team on large molecule specific assay operation for protein bioanalysis in support of pharmacokinetics focused on the following topics: setting up a balanced validation design, specificity testing, selectivity testing, dilutional linearity, hook effect, parallelism, and testing of robustness and ruggedness. The team additionally considered the impact of lipemia, hemolysis, and the presence of endogenous analyte on selectivity assessments as well as the occurrence of hook effect in study samples when no hook effect had been observed during pre-study validation. 相似文献
98.
99.
Arumugam N Sivakumar V Thanislass J Pillai KS Devaraj SN Devaraj H 《Toxicology letters》1999,104(3):189-194
Acute exposure of rats to acrolein (1 or 2 ppm) resulted in reduced levels of glutathione, ascorbic acid and alpha-tocopherol. The activities of catalase and glutathione peroxidase were reduced whereas an increase in the activities of superoxide dismutase was observed. This led to enhanced lipid peroxidation, which produced extensive lung damage as indicated by the elevated levels of the biochemical markers--angiotensin converting enzyme, lactate dehydrogenase, protein and lactate in the bronchoalveolar lavage. 相似文献
100.
Sharma AK Agarwal V Kumar R Balasubramaniam A Mishra A Gupta R 《Acta poloniae pharmaceutica》2011,68(6):897-904
The seeds of Alangium salvifolium Linn. have been traditionally reported to exhibit a variety of biological activities, including antidiabetic, anticancer, diuretic, anti-inflammatory, antimicrobial, laxative, and antiepileptic activities. The objective of this study was to verify the traditional claims and to evaluate the seeds of Alangium salvifolium in various organic extracts to screen the antidiabetic, antiepileptic, analgesic and antiinflammatory activities. The chloroform, ethanol, and water extracts of Alangium salvifolium seeds were obtained and subjected for phytochemical screening and evaluated for their pharmacological activities. From the acute toxicity study it was observed that chloroform, ethanol, and aqueous extracts of Alangium salvifolium seeds are non-toxic at a fixed dose of 2000 mg/kg. Among all three extracts ethanol extracts exhibited significant (p < 0.01) antidiabetic, antiepileptic, analgesic and anti-inflammatory activities. The phytochemical analysis revealed the presence of alkaloids, glycosides, terpenoids, steroids and tannins. The results of present study verified the traditional claims made by ayurvedic practitioner. However, the chemical constituents responsible for the pharmacological activities remain to be investigated. 相似文献