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多糖是一类重要的生物大分子物质,具有抗肿瘤、抗病毒、抗氧化、免疫活性调节等生物活性。多糖的生物活性与其结构有直接关系,因而对多糖结构通过适当的方法进行修饰是目前多糖领域研究的重要方向之一。简要地阐述多糖的化学修饰方法(包括硫酸化、羧甲基化、乙酰化和磷酸化等)研究进展,以及修饰后对生物活性的影响,以期为新药发现提供依据。  相似文献   
3.
  1. High concentrations of endogenous oestradiol (E2) correlate with the proliferation of cancer cells. Resveratrol (a dietary chemopreventive agent) at high concentrations has an anti-oestrogenic effect. E2 and resveratrol are conjugated via common uridine diphosphoglucuronosyltransferase (UGT) and sulfotransferases (SULT) enzymes.

  2. Experiments were conducted in MCF-7 mammalian cells stably expressing human SULT1A1 or SULT1E1 to observe the effect of resveratrol on E2-mediated cell proliferation. The combination of E2 and resveratrol did have a proliferative effect in cells expressing SULT1E1, but not in those expressing SULT1A1.

  3. The effect of resveratrol (1–500 μM) on the glucuronidation of E2 (0.25–2.25 μM) was characterized in human liver microsomes. The highest resveratrol concentration significantly decreased the intrinsic clearance of E2 glucuronidation.

  4. The results corroborate the reported significant inhibition of SULT1E1-mediated E2 sulfation in vitro by resveratrol. Thus, resveratrol may interact with E2 in vivo by inhibiting its conjugation.

  相似文献   
4.
  1. Dietary flavonoids catechin, epicatechin, eriodictyol, and hesperetin were investigated as substrates and inhibitors of human sulfotransferases (hSULTs). Purified recombinant proteins and human intestine cytosol were used as enzyme sources.

  2. hSULT1A1 and hSULT1A3 as well as human intestine cytosol can catalyse the sulfation of the investigated flavonoids.

  3. Sulfation of catechin, epicatechin, eriodictyol, and hesperetin by recombinant hSULTs showed substrate inhibition at high flavonoid concentrations.

  4. Hesperetin and eriodictyol are potent inhibitors of purified hSULT1A1, hSULT1A3, hSULT1E1, and hSULT2A1. Catechin and epicatechin inhibited hSULT1A1 and hSULT1A3, but not hSULT1E1 and hSULT2A1.

  5. The sulfation efficacy and potency of inhibition is related to the C-ring structure of flavonoids. These results suggest that dietary flavonoids may regulate human SULT activity and, therefore, affect the regulation of hormones and neurotransmitters, detoxification of drugs, and the bioactivation of pro- carcinogens and pro-mutagens.

  相似文献   
5.
大黄化学成分的药动学及其代谢的研究进展   总被引:1,自引:0,他引:1  
大黄是临床常用中药之一,当前关于其药动学和代谢研究主要关注游离蒽醌类成分。本文综述近年来关于大黄药动学与代谢的文献,梳理大黄化学成分的药动学研究(应用的分析技术、药味配伍对大黄蒽醌药动学影响、在不同机体状态下对大黄蒽醌药动学影响、大黄复方中蒽醌药动学研究),大黄化学成分在体内的代谢研究(应用的分析手段、借助的信息技术、体内的代谢途径)和大黄化学成分在体外的代谢研究。总结其吸收和代谢的特征,为该药物的后期研究奠定基础和提供参考。研究发现大黄蒽醌吸收快而消除慢,而药味配伍和机体状态都会影响其吸收和代谢。大黄化学成分的体内和体外代谢途径主要是葡萄糖醛酸化、硫酸酯化、甲基化等,其代谢物主要来源于蒽醌类成分。  相似文献   
6.
1.?Human cytosolic sulfotransferase 1B1 (SULT1B1) sulfates small phenolic compounds and bioactivates polycyclic aromatic hydrocarbons. To date, no SULT1B1 allelic variants have been well-characterized.

2.?While cloning SULT1B1 from human endometrial specimens, an allelic variant resulting in valine instead of leucine at the 145th amino acid position (L145V) was detected. NCBI reported this alteration as the highest frequency SULT1B1 allelic variant.

3.?L145V frequency comprised 9% of 37 mixed-population human patients and was specific to African Americans with an allelic frequency of 25%. Structurally, replacement of leucine with valine potentially destabilizes a conserved helix (α8) that forms the “floor” of both the substrate and PAPS binding domains. This destabilization results in altered kinetic properties including a four-fold decrease in affinity for PAP (3′, 5′-diphosphoadenosine). Kms for 3′-phosphoadenosine- 5′-phosphosulfate (PAPS) are similar; however, maximal turnover rate of the variant isoform (0.86?pmol/(min*μg)) is slower than wild-type (WT) SULT1B1 (1.26?pmol/(min*μg)). The L145V variant also displays altered kinetics toward small phenolic substrates, including a diminished p-nitrophenol Km and increased susceptibility to 1-naphthol substrate inhibition.

4.?No significant correlation between genotype and prostate or colorectal cancer was observed in patients; however, the variant isoform could underlie specific pathologies in sub-Saharan African carriers.  相似文献   
7.
宋见喜  任婷  王贺  牟莹莹  冯丽娟  孙新  佟海滨 《中草药》2017,48(24):5125-5129
目的优选高山红景天多糖(RSP)的最佳硫酸化修饰条件,提高RSP的抗氧化活性。方法利用氯磺酸-吡啶法对RSP进行了硫酸化修饰,并通过单因素实验确定了硫酸化反应的最佳工艺条件;应用红外光谱(IR)和扫描电子显微镜(SEM)对RSP和硫酸化高山红景天多糖(S-RSP)的理化性质进行了分析;通过测定RSP和S-RSP对1,1-二苯基-2-三硝基苯肼(DPPH)自由基的清除能力,考察了S-RSP的取代度(DS)与多糖抗氧化活性之间的关系。结果当氯磺酸与吡啶的体积比为1∶4、反应时间为2 h、反应温度为60℃时,制得的S-RSP的含硫量最大值为18.83%,取代度最大值为2.38。RSP经硫酸化修饰后,增强了其抗氧化活性,S-RSP的DS与DPPH自由基清除能力存在一定的正比例关系。结论氯磺酸与吡啶的体积比影响S-RSP的DS大小;RSP经硫酸化修饰后通过改变多糖的极性而增加了其抗氧化能力。  相似文献   
8.
Sulfation of resveratrol, a polyphenolic compound present in grapes and wine with anticancer and cardioprotective activities, was studied in human liver cytosol. In the presence of 3′-phosphoadenosine-5′-phosphosulfate, three metabolites (M1–3) whose structures were identified by mass spectrometry and NMR as trans-resveratrol-3-O-sulfate, trans-resveratrol-4′-O-sulfate, and trans-resveratrol-3-O-4′-O-disulfate, respectively. The kinetics of M1 formation in human liver cytosol exhibited an pattern of substrate inhibition with a Ki of 21.3?±?8.73?µM and a Vmax/Km of 1.63?±?0.41?µL?min?1mg?1 protein. Formation of M2 and M3 showed sigmoidal kinetics with about 56-fold higher Vmax/Km values for M3 than for M2 (2.23?±?0.14 and 0.04?±?0.01?µL?min?1?mg?1). Incubation in the presence of human recombinant sulfotransferases (SULTs) demonstrated that M1 is almost exclusively catalysed by SULT1A1 and only to a minor extent by SULT 1A2, 1A3 and 1E1, whereas M2 is selectively formed by SULT1A2. M3 is mainly catalysed by SULT1A2 and 1A3. In conclusion, the results elucidate the enzymatic pathways of resveratrol in human liver, which must be considered in humans following oral uptake of dietary resveratrol.  相似文献   
9.
马尾松花粉硫酸酯化多糖调控脾细胞[Ca~(2+)]_i的研究   总被引:1,自引:0,他引:1  
目的探讨马尾松花粉多糖硫酸酯化物(SPPM60-A)对小鼠脾细胞内游离钙离子浓度([Ca2+]i)调控的机制。方法热水浸提醇沉淀法提取马尾松花粉粗多糖,SephacrylS-400HR分离纯化,氯磺酸-吡啶法进行硫酸酯化,荧光分光光度计测定脾淋巴细胞[Ca2+]i。结果 LPS与SPPM60-A都能促进脾淋巴细胞[Ca2+]i升高,与对照相比升高率分别为11.7%和15.4%(P<0.01)。TAK-242、LY294002、U73122、低分子肝素与维拉帕米均可以抑制[Ca2+]i的升高。结论推测硫酸酯化马尾松花粉多糖可通过TLR4-PI3K-PLC-IP3R信号通路促进脾淋巴细胞内[Ca2+]i升高。  相似文献   
10.
The posttranslational sulfation of tyrosine has been though to be initiated by the recognition of specific consensus features by the sulfating enzyme tyrosylprotein sulfotransferase (TPST). However, using these recognition features to identify new tyrosine sulfation sites misses recently characterized sites that lack these features. Rigorous analysis of the amino acids surrounding the target tyrosin using the position-specific scoring matrix (PSSM) demonstrates that a consensus sequence does not contain all the information necessary to predict tyrosine sulfation. Instead, accurate prediction requires consideration of all residues within five amino acids on either side of the target tyrosine. These results support the notion that secondary structure is the major determinant of sulfation and that other residues within the sulfation site can compensate for deviations from commonly observed features. This view implies that specific consensus features are not critical for TPST substrate recognition but that TPST may instead broadly recognize any sufficiently exposed tyrosine residue.  相似文献   
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