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《Biomedicine & Pharmacotherapy》2014,68(8):1149-1159
Anthracycline chemotherapy is often used in the treatment of various malignancies. Its application, however, encounters several limitations due to development of serious side effects, mainly cardiotoxicity and may be ineffective due to multidrug resistance (MDR). Many different compounds have been evaluated as poorly effective in the protection against anthracycline side effects and in the prevention from MDR. Thus, continuous investigational efforts are necessary to find valuable protectants and the flavonoid quercetin (Q) seems to be a promising candidate. It is present in relatively high amounts in a human diet and the lack of its toxicity, including genotoxicity has been confirmed. The structure of Q favours its high antioxidant activity, the potential to inhibit the activity of oxidative enzymes and to interact with membrane transporter proteins responsible for development of MDR, e.g. P-glycoprotein. Furthermore, Q can influence cellular signalling and gene expression, and thus, alter response to exogenous genotoxicants and oxidative stress in normal cells. It accounts for its chemopreventive and anticancer properties. Overall, these properties might indicate the possibility of application of Q as cardioprotectant during anthracycline chemotherapy. Moreover, numerous biological properties displayed by Q might possibly result in the reversal of MDR in tumour cells and improve the efficacy of chemotherapy. However, these beneficial effects towards anthracycline-induced complications of chemotherapy have to be further explored and confirmed both in animal and clinical studies. Concurrently, investigations aimed at improvement of the bioavailability of Q and further elucidation of its metabolism after application in combination with anthracyclines are needed. 相似文献
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目的探讨赖氨酰氧化酶(lysyl oxidase,LOX)、血管内皮因子(vascular endothelial growth factor,VEGF)在胃癌进展中的作用关系。方法收集手术切除的新鲜胃癌组织65例,采用Western blotting方法检测胃癌组织中的LOX、VEGF蛋白表达,并比较二者在T1T2与T3T4胃癌组织、有无淋巴结转移胃癌组织中的关系。结果 (1)LOX在T3T4胃癌中的相对表达量为0.6003±0.1279,在T1T2胃癌中的相对表达量为0.4278±0.1437,差异有统计学意义(P0.05);(2)VEGF在T3T4胃癌中的相对表达量为0.6975±0.1639,在T1T2胃癌中的相对表达量为0.4263±0.1128,差异有统计学意义(P0.05);(3)LOX在伴有淋巴结转移的胃癌中的相对表达量为0.6827±0.1987,在无淋巴结转移的胃癌中的相对表达量为0.4235±0.1763,差异有统计学意义(P0.05);(4)VEGF在伴有淋巴结转移的胃癌中的相对表达量为0.6769±0.1659,在无淋巴结转移的胃癌中的相对表达量为0.4128±0.1471,差异有统计学意义(P0.05);(5)在T1T2和T3T4胃癌组织中,LOX与VEGF的表达水平呈正相关(r=0.735,P0.05),在有淋巴结转移和无淋巴结转移的胃癌组织中,LOX与VEGF的表达水平也呈正相关(r=0.914,P0.05)。结论 T3T4胃癌中LOX与VEGF的表达水平明显高于T1T2胃癌,在有淋巴结转移的胃癌组织中,LOX与VEGF的表达水平明显高于无淋巴结转移的胃癌组织中,且LOX与VEGF表达呈正相关;LOX与VEGF在胃癌的进展中有促进作用,并且相互协同。 相似文献
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Nathalie Mercier Pascal Challande Mary Osborne-Pellegrin 《Toxicology and applied pharmacology》2009,239(3):258-267
To investigate a putative role for semicarbazide-sensitive amine oxidase (SSAO) in arterial extracellular matrix (ECM) organization, we compared arteries of growing Brown Norway (BN) rats after chronic administration of semicarbazide (SCZ) and β-aminopropionitrile (BAPN), two inhibitors with different properties and relative specificities for SSAO and lysyl oxidase (LOX). The BN model is particularly well adapted to evaluating effects of toxic compounds on the arterial elastic network. We measured aortic LOX and SSAO activities and quantified several ECM parameters. After a pilot study comparing doses previously studied and testing for additivity, we studied low and high equimolar doses of SCZ and BAPN. Both compounds similarly inhibited LOX, whereas SCZ inhibited SSAO far more effectively than BAPN. Both decreased carotid wall rupture pressure, increased tail tendon collagen solubility, decreased aortic insoluble elastin (% dry weight) and dose-dependently increased defects in the internal elastic lamina of abdominal aorta, iliac and renal arteries. Our results suggest that either these effects are mediated by LOX inhibition, SCZ being slightly more effective than BAPN in our conditions, or SSAO acts similarly to and in synergy with LOX on ECM, the greater SCZ effect reflecting the simultaneous inhibition of both enzymes. However, the high SCZ dose increased aortic collagen and ECM proteins other than insoluble elastin markedly more than did equimolar BAPN, possibly revealing a specific effect of SSAO inhibition. To discriminate between the two above possibilities, and to demonstrate unequivocally a specific effect of SSAO inhibition on ECM formation or organization, we must await availability of more specific inhibitors. 相似文献
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Background
The role of lectin‐like oxidized low‐density lipoprotein receptor (LOX)‐1 has been implicated in the pathogenesis of different diseases, including atherosclerosis, hypertension, obesity, diabetes mellitus and metabolic syndrome. To date, several studies aimed at partially investigating the mechanistic role of LOX‐1 in these various pathologies. Still, so far, the precise signal transduction pathways involving LOX‐1 have not yet been elucidated.Materials and Methods
The most recent data published by the authors as well as others concerning different pathways involving LOX‐1 are collected to formulate the presented updated review.Results
One of the most prominent pathways highlighted in the present review is the relationship of LOX‐1 to NADPH oxidase that acts as a major source of harmful free radicals causing oxidative stress in blood vessels. Other pathways involve lipid and glucose metabolism‐mediated signal transduction.Discussion
The modulatory role of LOX‐1 on nitric oxide and renin/angiotensin systems as well as on fibrosis, apoptosis and inflammatory pathways is discussed.Conclusion
The current review revisits LOX‐1 and its related pathways, implicating LOX‐1 as a target for ameliorating various pathological conditions. 相似文献79.
Aroke S. Ahmed Lyndy J. McGaw Esameldin E. ElgorashiVinasan Naidoo Jacobus N. Eloff 《Journal of ethnopharmacology》2014
Ethnopharmacological importance
Gastrointestinal disorders and infections are the major pathoaetiologies of diarrhoea causing many problems in human health and animal production. Many Combretum species are used in traditional medicine to treat infectious diseases including diarrhoea and many other ailments by rural people in Africa and Asia. Much of the work done to date on this genus was on the non-polar or intermediate polarity components. Some parameters that may cause diarrhoea and the evaluation of more polar extracts have apparently not been investigated.Aims
The polar components were extracted and fractionated by solvent–solvent fractionation to yield fractions with different polarities. The activity of these fractions on different parameters that could be involved in factors associated with diarrhoea was investigated. The cytotoxic activities of the extracts were also determined to evaluate the potential of these extracts to combat diarrhoea in production animals.Materials and methods
Phenolic-enriched leaf extracts of Combretum bracteosum (COB), Combretum padoides (COP), Combretum vendae (COV) and Combretum woodii (COW) were obtained by extracting with a mixture of 70% acetone acidified with 1% HCl and n-hexane. Acetone was removed from a portion of the 70% acetone extract and it was sequentially treated by solvent–solvent fractionation with dichloromethane, ethyl acetate, and butanol to yield fractions with a large variation in polarity. The phenolic constituents of the extracts and fractions were determined using standard procedures The antioxidant activities were determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH); 2,2′-azino-bis (3-ethylbenzothiazoline)-6-sulphonic acid (ABTS+) radical scavenging, ferric reducing antioxidant power (FRAP) methods and lipid peroxidation inhibitory capacity standard methods. The ferric reducing antioxidant activities of the fractions were also determined. The minimum inhibitory concentrations (MICs) of the crude extracts and fractions against four bacterial and three fungal strains were assessed with a microplate serial dilution method. Cyclooxygenase (COX) and lipoxygenase (LOX) enzyme inhibitory assays and cytotoxicity studies against Vero cells were also carried out.Result
Some of the fractions had much higher antioxidant activity than the positive controls. The average EC50 values of the extracts for the DPPH and ABTS antioxidant assays were 0.21–12 µg/ml (COP), 0.25–16 µg/ml (COV), 0.33–9.41 µg/ml (COW) and 4.97–85 µg/ml (COB) respectively while the mean EC50 values for the positive controls ascorbic acid and trolox were 1.28–1.51 and 1.02–1.19 µg/ml respectively. All the crude extracts inhibited lipid peroxidation of linoleic acid by more than 80% at a concentration of 64 µg/ml. COP had the highest antibacterial activity with MICs ranging between 19–2500 µg/ml, followed by COV with MICs ranging between 39–625 µg/ml; COW and COB had similar MICs ranging between 39–2500 µg/ml. COP also had the highest antifungal activity with MICs between 19–625 µg/ml. The MIC for COW and COV ranged from 19 to 1250 µg/ml. COB had the lowest antifungal activity (MIC values were between 39 and 625 µg/ml). In general non-polar fractions had a high antimicrobial activity and polar fractions had a high antioxidant activity. The extracts had no activity against COX 1 and 2 enzymes in the anti-inflammatory assay but had good lipoxygenase inhibition. The crude extracts had high concentration of hydrolysable tannin (gallotannin). A good correlation (R2= 0.99) was found between the antioxidant activity and total tannin content indicating that, gallotannins may be responsible for the antioxidant activity.Conclusion
The results obtained in this study with more polar extracts indicate that the use of extracts of these plant species as antidiarrhoeal agents may have a scientific basis. The extractant used here extracted a much higher percentage of the phytochemicals than acetone. It was better for isolating antioxidant compounds (polar) but not good for isolating antimicrobial compounds (non-polar) from the same species compared to acetone, ethyl acetate, dichloromethane, and hexane. 相似文献80.
Interactive Effect of Bisphenol A (BPA) Exposure with -22G/C Polymorphism in LOX Gene on the Risk of Osteosarcoma
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《Asian Pacific journal of cancer prevention》2013,14(6):3805-3808
Background: Osteosarcomas have many established risk factors, both genetic and environmental, but bythemselves these explain only part of the total cancer incidence. Bisphenol A (BPA) is an environmental estrogenassociated with risk of several kinds of tumour. The lysyl oxidase gene (LOX) may also contribute to risk oftumours including osteosarcomas. Here, we investigated possible interactions of BPA and a LOX polymorphism onthe risk of osteosarcoma. Method: The present hospital-based case-control study included 106 cancer patients and112 controls from a Chinese population. Internal burden of BPA exposure was assessed using high-performanceliquid chromatography–mass spectrometry (HPLC-MS) method. Genotypes were determined using PCR-RFLPmethods. Results: Compared with those in low BPA exposure group, subjects with BPA more than or equal tomedian value had significant increased risk of osteosarcoma among subjects who carried GC or CC genotypes.A significant interaction with BPA level and the -22G/C polymorphism was observed for osteosarcoma overall,osteosarcoma affecting knee and osteosarcoma affecting hip, as Pforinteraction = 0.036 for osteosarcoma overall;Pforinteraction = 0.024 for osteosarcoma affecting knee; and Pforinteraction = 0.017 for osteosarcoma affecting hip.Conclusions: The results suggest that BPA exposure interacts with the -22G/C polymorphism of the LOX geneto increase the risk of osteosarcoma. 相似文献