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81.
Synthesis, antioxidant activity, and quantitative structure–activity relationship (QSAR) of 25 of chalcone derivatives is
reported here. They were synthesized by Claisen–Schmidt reaction and were characterized by FTIR, NMR, and mass spectroscopy.
Antioxidant activity is evaluated through four different methods namely, superoxide radical-scavenging, hydrogen peroxide
scavenging, reducing power, and DPPH radical-scavenging assays. Generally, compounds with –SCH3 and –OCH3 in the para position of the A-ring and –OH in the B-ring were more active than others. In few cases some of the compounds were more active
than ascorbic acid or butylated hydroxytoluene. QSAR was developed correlating the antioxidant activity with the structural
features of the compounds and the predictive capability of the models was estimated using internal and external validation
methods. All the predictions were within the 99% confidence level. Spatial, structural, and lipophilic properties of the compounds
determine their antioxidant properties. 相似文献
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84.
Thalidomide attenuates nitric oxide-driven angiogenesis by interacting with soluble guanylyl cyclase
Syamantak Majumder Megha Rajaram Ajit Muley Himabindu S Reddy KP Tamilarasan Gopi Krishna Kolluru Swaraj Sinha Jamila H Siamwala Ravi Gupta R Ilavarasan S Venkataraman KC Sivakumar Sharmila Anishetty Pradeep G Kumar Suvro Chatterjee 《British journal of pharmacology》2009,158(7):1720-1734
Background and purpose:
Nitric oxide (NO) promotes angiogenesis by activating endothelial cells. Thalidomide arrests angiogenesis by interacting with the NO pathway, but its putative targets are not known. Here, we have attempted to identify these targets.Experimental approach:
Cell-based angiogenesis assays (wound healing of monolayers and tube formation in ECV304, EAhy926 and bovine arterial endothelial cells), along with ex vivo and in vivo angiogenesis assays, were used to explore interactions between thalidomide and NO. We also carried out in silico homology modelling and docking studies to elucidate possible molecular interactions of thalidomide and soluble guanylyl cyclase (sGC).Key results:
Thalidomide inhibited pro-angiogenic functions in endothelial cell cultures, whereas 8-bromo-cGMP, sildenafil (a phosphodiesterase inhibitor) or a NO donor [sodium nitroprusside (SNP)] increased these functions. The inhibitory effects of thalidomide were reversed by adding 8-bromo-cGMP or sildenafil, but not by SNP. Immunoassays showed a concentration-dependent decrease of cGMP in endothelial cells with thalidomide, without affecting the expression level of sGC protein. These results suggested that thalidomide inhibited the activity of sGC. Molecular modelling and docking experiments revealed that thalidomide could interact with the catalytic domain of sGC, which would explain the inhibitory effects of thalidomide on NO-dependent angiogenesis.Conclusion and implications:
Our results showed that thalidomide interacted with sGC, suppressing cGMP levels in endothelial cells, thus exerting its anti-angiogenic effects. These results could lead to the formulation of thalidomide-based drugs to curb angiogenesis by targeting sGC. 相似文献85.
86.
Sathasivam S 《Nature clinical practice. Neurology》2008,4(6):317-327
In chronic autoimmune conditions such as myasthenia gravis (MG), immunosuppression--usually long-term--is often necessary. The mechanisms of action of immunosuppressant drugs in MG fall into three main categories: inhibition of the cell cycle (azathioprine, cyclophosphamide, methotrexate and mycophenolate mofetil), immunosuppression of T cells (steroids, ciclosporin and tacrolimus), and B-cell depletion (rituximab). Data on immunosuppressant drugs in MG derive mainly from clinical experience, observational studies and expert opinion. The main drawbacks of the randomized evidence are the small size of most drug trials, variations in study design, and a lack of head-to-head studies. It is therefore difficult to determine the relative efficacy of each immunosuppressant. Oral prednisolone, usually started at a low dose on an alternate-day regimen, and gradually increased, is the recommended first-choice short-term immunosuppressant. Long-term immunosuppression regimens vary between different countries and physicians. Azathioprine is often the first-choice drug for long-term immunosuppression, and it is usually started together with steroids to allow tapering of steroids to the lowest dose possible. Methotrexate, mycophenolate mofetil or tacrolimus should be considered in patients who are intolerant of or unresponsive to azathioprine. Ciclosporin and cyclophosphamide should only be considered as a last resort, as these drugs can cause serious adverse events. Data on rituximab use in MG are sparse, but the initial results are promising. 相似文献
87.
Reduced mitochondrial coenzyme Q10 levels in HepG2 cells treated with high-dose simvastatin: a possible role in statin-induced hepatotoxicity? 总被引:1,自引:0,他引:1
Tavintharan S Ong CN Jeyaseelan K Sivakumar M Lim SC Sum CF 《Toxicology and applied pharmacology》2007,223(2):173-179
Lowering of low-density lipoprotein cholesterol is well achieved by 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins). Statins inhibit the conversion of HMG-CoA to mevalonate, a precursor for cholesterol and coenzyme Q10 (CoQ10). In HepG2 cells, simvastatin decreased mitochondrial CoQ10 levels, and at higher concentrations was associated with a moderately higher degree of cell death, increased DNA oxidative damage and a reduction in ATP synthesis. Supplementation of CoQ10, reduced cell death and DNA oxidative stress, and increased ATP synthesis. It is suggested that CoQ10 deficiency plays an important role in statin-induced hepatopathy, and that CoQ10 supplementation protects HepG2 cells from this complication. 相似文献
88.
Sanger GJ Tuladhar BR Brown J Aziz E Sivakumar D Furness JB 《Autonomic & autacoid pharmacology》2007,27(2):105-111
1. NK(3) tachykinin receptors mediate slow excitatory transmission in the enteric nervous system and play a role in reflexes induced by the intestinal stretch or mucosal compression. However, there is little evidence to suggest that these receptors are important in peristalsis. We have examined the effects of the NK(3) receptor antagonist, talnetant, on peristalsis in guinea-pig isolated ileum induced by optimal and by supra-maximal distension pressures. 2. At the guinea-pig NK(3) receptor, talnetant was shown to have high affinity (pK(B) 8.8) and selectivity over the guinea-pig NK(1) and NK(2) receptors. 3. Peristaltic waves in the ileum elicited by optimal distension pressures (1-3 cmH(2)O) were unaffected by talnetant at a supra-maximal concentration (250 nm). 4. Distension at a higher pressure (4 cmH(2)O) induced peristalsis in which there was incomplete closure of the lumen during each peristaltic wave and an increase in the periods of inactivity observed between bursts of peristaltic activity. The addition of talnetant (250 nm) increased the number of peristaltic events by reducing these periods of inactivity and thus, increased the productivity of the peristaltic reflex. 5. The data suggest that NK(3) receptors are not involved in the modulation of peristaltic movements by physiological stimuli, but they may have a role in modulation of reflexes in extreme or pathological conditions. 相似文献
89.
Vijayaraghavalu S Raghavan D Labhasetwar V 《Current opinion in investigational drugs (London, England : 2000)》2007,8(6):477-484
Despite decades of research, progress in cancer chemotherapy is relatively slow, hampered, in part, by the lack of appropriate mechanisms to deliver anticancer drugs selectively to tumor tissues. This is a challenging task, as various cellular, anatomical and physiological barriers impede effective delivery of drugs to tumors. Systemic or oral administration can cause severe toxicity, which limits the therapeutic potential of anticancer drugs. Therefore, the most important goal of drug delivery is to minimize the exposure of normal tissues to these drugs while maintaining their therapeutic concentration in tumors. Furthermore, the risk of subtherapeutic dosing of anticancer drugs is significant as tumors may develop drug resistance as a result of biochemical changes, drug export mechanisms, or limitations in mechanisms of cellular drug importation. As the field of cancer nanomedicine advances, it is anticipated that many drug delivery-related issues concerning cancer chemotherapeutics will be resolved. This review discusses the current status of nanoparticle-mediated cancer drug delivery, challenges to its utilization, and potential implications of its use in cancer therapy. 相似文献
90.
Kumar RS Sunderam RS Sivakumar T Sivakumar P Sureshkumar R Kanagasabi R Vijaya M Perumal BP Gupta M Mazumdar UK Kumar MS Kumar KA 《The American journal of Chinese medicine》2007,35(1):103-114
The aim of this study is to investigate the antioxidant defense system induced by the methanol extract of Bauhinia racemosa L.(MEBR) against N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis in Wister albino rats. The effects of MEBR on surface visible macroscopic (Morphometry) liver lesions (neoplastic nodules) and the levels of serum enzymes, lipid peroxidation and antioxidants were evaluated in NDEA-induced hepatocarcinogenesis in rats. In rats treated, with NDEA, significantly elevated levels of serum enzymes (SGOT, SGPT and ALP), bilirubin and decreased levels of protein and uric acid were observed. Significantly elevated amount of malondialdehyde (MDA), the end product of lipidperoxidation, indicated higher levels of lipid peroxidation, which was accompanied by significantly decreased levels of antioxidants like vitamin C, vitamin E, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). Administration of MEBR was able to suppress nodule development/hepatocellular lesion formation in rats. The extract treatment increases in antioxidant levels and dramatic decreases in lipid peroxidation levels. MEBR also produced a protective effect by decreasing the level of serum enzymes, bilirubin and increased the protein and uric acid levels. The results suggest that MEBR exert chemopreventive effects by suppressing nodule development and decreasing lipid peroxidation and enhancing the levels of antioxidants in NDEA carcinogenesis by reducing the formation of free radicals. 相似文献