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High-throughput gene expression technologies such as microarrays have been utilized in a variety of scientific applications. Most of the work has been done on assessing univariate associations between gene expression profiles with clinical outcome (variable selection) or on developing classification procedures with gene expression data (supervised learning). We consider a hybrid variable selection/classification approach that is based on linear combinations of the gene expression profiles that maximize an accuracy measure summarized using the receiver operating characteristic curve. Under a specific probability model, this leads to the consideration of linear discriminant functions. We incorporate an automated variable selection approach using LASSO. An equivalence between LASSO estimation with support vector machines allows for model fitting using standard software. We apply the proposed method to simulated data as well as data from a recently published prostate cancer study. 相似文献
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Arul V Gopinath D Gomathi K Jayakumar R 《Journal of biomedical materials research. Part B, Applied biomaterials》2005,73(2):383-391
Matrikines are small peptide fragments of extracellular matrix proteins that display potent tissue repair activities. Difficulties in achieving sustained delivery of bioactive concentration of matrikines in the affected area limits their therapeutic use. The present study evaluates the effects biotinylated matrikine peptide (bio-glycyl-histidyl-lysine) incorporated collagen membrane for dermal wound healing processes in rats. Biotinylated peptide incorporated collagen matrix (PIC) showed better healing when compared to wounds treated with collagen matrix [CF (collagen film)] and without collagen [CR (control)]. Binding studies indicate that biotinylated GHK (Bio-GHK) binds effectively to the collagen matrix and red blood cell (RBC) membrane when compared with t-butyloxycarbonyl substituted GHK (Boc-GHK). Wound contraction, increased cell proliferation, and high expression of antioxidant enzymes in PIC treated group indicate enhanced wound healing activity when compared to CF and CR groups. Interestingly Bio-GHK incorporated collagen increases the copper concentration by ninefold at the wound site indicating the wound healing property of Bio-GHK can also be linked with both copper localization and matrikine activities. These results demonstrate the possibility of using Bio-GHK incorporated collagen film as a therapeutic agent in the wound healing process. 相似文献
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Jacques H Gascon A Arul J Boudreau A Lavigne C Bergeron J 《The American journal of clinical nutrition》1999,70(6):983-991
BACKGROUND: A modified milk fat with reduced cholesterol was developed by fractionation technology. OBJECTIVE: The effect of this modified milk fat on the lipoprotein profile of 21 normolipidemic men was compared with that of regular milk fat and nonhydrogenated margarine. DESIGN: A crossover design was used for the administration of the 3 experimental diets, which provided 13240 kJ as 16% protein, 51% carbohydrates, 33-34% lipids, and 21 g fiber/d. The ratio of polyunsaturated to saturated fat was 1.3:1 for the margarine diet and 0.3:1 for the milk-fat diets. The cholesterol content of the modified milk-fat and margarine diets was similar (248 and 254 mg/d, respectively), but was significantly higher (428 mg/d) for the regular milk-fat diet. RESULTS: Modified and regular milk fats did not change plasma total and LDL cholesterol significantly, but margarine did (P < 0.01). Furthermore, modified milk fat maintained initial HDL(2)-cholesterol concentrations, but margarine reduced this variable significantly (P < 0.05). These results can be explained by the lower ratio of polyunsaturated to saturated fat in the modified and regular milk-fat diets than in the margarine diet. Men who ingested modified milk fat had significantly (P < 0.05) lower total and VLDL-triacylglycerol and VLDL-cholesterol concentrations than did those who ingested either regular milk fat or margarine. This may have been, in part, because of the lower intestinal fat absorption with modified milk fat than with regular milk fat and margarine arising from changes in the melting properties of milk fat with fractionation. CONCLUSION: A reduction in plasma triacylglycerol concentrations after the consumption of modified milk fat may prevent the onset of hypertriacylglycerolemia. 相似文献
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Arul Prakash Francis Thiyagarajan Devasena Selvam Ganapathy Venkata Rajsekhar Palla Prakhya Balakrishna Murthy Sundara Ramaprabhu 《Nanomedicine : nanotechnology, biology, and medicine》2018,14(6):1809-1822
Human beings and ecosystems are being possibly exposed to CNTs, as there is a rise in global production rate of carbon nanotubes (CNTs). This may affect the health of humans and increases the environmental risk. We have already reported the pulmonary toxicity due to the inhalation of MWCNTs. We claim that a compound with anti-inflammatory and antioxidant activity may ameliorate the CNT-induced toxic effect. With this view, we have investigated the ameliorative effect of intravenously-administered nano bis-demethoxy curcumin analog (NBDMCA) against MWCNTs-induced inhalation toxicity by examining the lung histopathology for inflammatory cell dynamics, pulmonary remodeling and estimating the inflammatory biomarkers in the broncho-alveolar lavage fluid. We observed that NBDMCA could ameliorate the injury as evidenced by the decline in the levels of markers of inflammation, cell damage, and the histopathological changes induced by MWCNTs. We conclude that NBDMCA may be used to reduce the risk of MWCNTs-induced inhalation toxicity. 相似文献
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Arul Prakash Francis A. Jayakrishnan 《Journal of biomaterials science. Polymer edition》2013,24(16):1471-1488
AbstractAs mannose receptors are known to be over-expressed in cancer cells, we synthesized polymannose-doxorubicin (PM-DOX) conjugates with the objective of targeting the drug to cancer cells. DOX was conjugated to oxidized PM through Schiff’s linkages to obtain PM-DOX conjugates. In order to examine the superior targeting efficacy of PM-DOX conjugate, sodium alginate (SA) was conjugated to DOX by similar chemistry and compared with PM-DOX conjugate. The cytotoxicity of the conjugates was investigated in A549 cell lines using MTT Assay and the cell uptake and retention studies, were performed using flow cytometry and cell imaging. In vitro drug release studies with both PM-DOX and SA-DOX conjugates showed an initial burst release of DOX up to 37–39% at 1?h, followed by a steady release up to 58–62% at 24?h in human plasma while negligible release was observed in phosphate buffered saline. The conjugates exhibited negligible hemolytic potential to human erythrocytes compared to free DOX. The PM-DOX conjugate showed better cytotoxic potential against A549 cells at lower concentration (equivalent to 0.27?μg/mL of DOX) at 72?h compared to free DOX and SA-DOX conjugate. Further, PM-DOX conjugate showed enhanced uptake by the cells in comparison with SA-DOX conjugate thereby confirming the target specificity of PM to the cancer cells. 相似文献
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Demichelis F Setlur SR Banerjee S Chakravarty D Chen JY Chen CX Huang J Beltran H Oldridge DA Kitabayashi N Stenzel B Schaefer G Horninger W Bektic J Chinnaiyan AM Goldenberg S Siddiqui J Regan MM Kearney M Soong TD Rickman DS Elemento O Wei JT Scherr DS Sanda MA Bartsch G Lee C Klocker H Rubin MA 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(17):6686-6691
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Croft AP Situnayake D Khair O Giovanni G Carruthers D Sivaguru A Gordon C 《Clinical rheumatology》2012,31(6):1013-1018
Chronic progressive multisystem granulomatous disease is seen in 10-30% of patients with sarcoidosis and can result in end organ damage. Corticosteroids are the mainstay of treatment with the addition of cytotoxic agents in severe cases. Some patients are refractory to such treatment and, therefore, management is a challenge. There is currently limited evidence for biological agents such as infliximab, a monoclonal anti-tumor necrosis factor-α antibody in the treatment of multisystem sarcoidosis. We report outcomes of three patients with extensive multisystem sarcoidosis refractory to conventional treatment and treated at our center. Clinical assessment and radiographic imaging were used to assess the response to infliximab treatment. Infliximab therapy induced clinical remission in all three patients, and this clinical response correlated with radiographic evidence of the resolution of granulomatous disease. Serum ACE level was reduced in all cases, and daily steroid dosage was reduced. We propose that infliximab can be an effective treatment in patients with multisystem complex sarcoidosis refractory to conventional drug therapy and can result in sustained clinical remission. Our experience supports the urgent need for randomized controlled clinical trials of anti-TNF therapy in refractory systemic sarcoidosis. 相似文献
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