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《Biochemical pharmacology》2015,94(4):482-495
Platelet-activating factor (PAF) is a well-known phospholipid that mediates acute inflammatory responses. In the present study, we investigated whether PAF/PAF receptor signaling contributed to chronic inflammation in the white adipose tissue (WAT) of PAF receptor-knockout (PAFR-KO) mice. Body and epididymal WAT weights were higher in PAFR-KO mice fed a high-fat diet (HFD) than in wild-type (WT) mice. TNF-α mRNA expression levels in epididymal WAT and the infiltration of CD11c-positive macrophages into epididymal WAT, which led to chronic inflammation, were also elevated in HFD-fed PAFR-KO mice. HFD-fed PAFR-KO mice had higher levels of fasting serum glucose than HFD-fed WT mice as well as impaired glucose tolerance. Although PAF receptor signaling up-regulated the expression of TNF-α and lipopolysaccharide induced the expression of acyl-CoA:lysophosphatidylcholine acyltransferase 2 (LPCAT2) mRNA in bone marrow-derived macrophages, no significant differences were observed in the expression of LPCAT2 mRNA and PAF levels in epididymal WAT between HFD-fed mice and normal diet-fed mice. In addition to our previous finding in which energy expenditure in PAF receptor (PAFR)-deficient mice was low due to impaired brown adipose tissue function, the present study demonstrated that PAF/PAF receptor signaling up-regulated the expression of Ucp1 mRNA, which is essential for cellular thermogenesis, in 3T3-L1 adipocytes. We concluded that the marked accumulation of abdominal fat due to HFD feeding led to more severe chronic inflammation in WAT, which is associated with glucose metabolism disorders, in PAFR-KO mice than in WT mice, and PAF/PAF receptor signaling may regulate energy expenditure and adiposity.  相似文献   
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A new l-amino acid oxidase (designated as DRS-LAAO) was purified from Daboia russellii siamensis venom by ion-exchange, gel filtration and affinity chromatographies. DRS-LAAO is a homodimeric enzyme with a molecular weight of 120.0 kDa as measured by size exclusion chromatography and the monomeric molecular weight of 58.0 kDa as measured by SDS-PAGE under both non-reducing and reducing conditions. The N-terminal amino acid sequence (ADDKNPLEECFREDD) of DRS-LAAO shares high identity with other snake venom l-amino acid oxidases, especially with those isolated from viperid venoms. The enzyme displayed high specificity towards hydrophobic l-amino acids. The best substrate of DRS-LAAO was L-Leu followed by L-Phe and L-Ile, while five substrates — L-Pro, L-Asn, L-Gly, L-Ser and L-Cys were not oxidized. Optimal pH of DRS-LAAO was 8.8. The enzyme showed no hemorrhagic activity even at a dosage of 55.0 μg. DRS-LAAO dose-dependently inhibited platelet aggregation induced by ADP (83.33 μM) and TMVA (55.0 nM) with an IC50 value of 32.8 μg/ml and 32.3 μg/ml, respectively. The minimum inhibitory concentrations (MICs) of DRS-LAAO against Staphylococci aureus (ATCC 25923), Pseudomonas aeruginosa (ATCC 27853) and Escherichia coli (ATCC 25922) were 9.0, 144.0 and 288.0 μg/ml, respectively. The minimum bactericidal concentrations (MBCs) of the enzyme for these strains were twice of the MIC values. These results showed that DRS-LAAO had the strongest antimicrobial activity against S. aureus among these three international standard stains. Antibacterial-activities of DRS-LAAO against eight clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates were also tested. The MICs of DRS-LAAO against these isolates ranged from 4.5 to 36.0 μg/ml. And the MBCs of the enzyme against these isolates ranged from 9.0 to 72.0 μg/ml.  相似文献   
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We have previously shown that non-structural protein p35, encoded by Scylla serrata reovirus (SsRV) S10, may act as a viroporin. To characterize the role of p35 protein in the modulation of cellular function, a yeast two-hybrid system was used to screen a cDNA library derived from S. serrata to find its interacting partner. Protein interactions were confirmed in vitro by GST pull-down. Full cDNAs of p35 interactors were cloned by the rapid amplification of cDNA ends. After two-hybrid library screening, we isolated partial cDNAs encoding hemocyanin, cryptocyanin, and TAX1BP1. Interaction of p35 with each of hemocyanin, cryptocyanin, and TAX1BP1 was confirmed by GST pull-down. The full-length cDNA fragments of hemocyanin, cryptocyanin, and TAX1BP1 were 2287, 2422, and 3437 bp, respectively, and they encoded three putative proteins with molecular masses of ~76.9, ~79.2, and ~107.2 kDa, respectively. This study casts new light on the function and physiological significance of p35 during the SsRV replication cycle.  相似文献   
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研究黄精多糖(PP)对环磷酰胺(Cy)所致免疫抑制小鼠免疫功能的调节作用。将40只小鼠随机分为5组:正常、模型、PP低、中、高(100,400,800 mg/kg)剂量组。每日灌胃给药饲养20 d,期间于d 3,d 6,除正常组外,其它各组按6 mg/kg腹腔注射Cy。测定器官与体液相关免疫指标。结果表明:与正常组比,模型组造模成功。与模型组相比,PP给药组能显著修复免疫抑制小鼠的DTH反应、脏器指数、吞噬指数、溶血素指数(P<0.05),且呈明显的剂量依赖性;高剂量PP给药组小鼠血清中SOD活性得到显著恢复(231.71±7.75)U/mL、MDA含量显著降低(6.20±0.65)nmol/mL,到达或超过了正常组小鼠相应指标。因此,PP能有效逆转和修复由Cy所致的免疫抑制小鼠的免疫功能,可开发为肿瘤放化疗的辅助治疗剂。  相似文献   
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通过饲喂高脂饲料,建立小鼠营养性肥胖模型,研究羊栖菜中岩藻黄质提取物(SFFE)的减肥作用。实验选取ICR雄性小鼠饲喂高脂饲料为模型组,基础饲料为对照组,建模后分别给予模型高、中、低剂量组3.0、1.5、0.3mg的SFFE/d灌胃,21 d后测定小鼠的体重、Lee,s指数、脏器系数及血清生化指标。结果表明,建立高脂饲料模型组平均增重率达(32.03±2.02)%,体重显著高于基础饲料对照组(P<0.05);饲喂高、中、低剂量SFFE后体重、Lee,s指数显著低于模型空白组小鼠(P<0.05);各模型组与对照组小鼠血清中TC、TG、HDL-C、LDL-C指标,脏器系数指标均无差异;灌服SFFE高、中、低剂量组小鼠血清中GLU含量均显著低于模型空白组(P<0.05),且与基础饲料对照组无差异(P>0.05)。实验提示SFFE具有良好的减肥、调节血糖功能作用,为SFFE减肥产品开发奠定了理论基础。  相似文献   
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Gingival health and salivary gland function were evaluated for a period of 5 years in 14 patients who received head and neck irradiation for nasopharyngeal carcinoma (seven patients; total dose >60 Gy, nasopharyngeal field) and Hodgkin's lymphoma (seven patients; total dose <50 Gy, “mantle” field). Plaque index (PII), bleeding index (BI), gingival recession (GR), whole saliva flow rate (WSFR), left parotid sialographic morphology, and salivary gland radioisotopic activity were assessed immediately before radiotherapy and annually thereafter. The nasopharyngeal group had perfect correlation between postradiation depression of WSFR and the sialographic and scintigraphic scores (R = −1.00 and −0.96, respectively). The degree of gland dysfunction correlated negatively with BI and the BI/PII ratio (r = #x02212;0.497) and with GR (r = 0.681). The same correlations were noted in the group with Hodgkin's lymphoma during the first 3 years of follow-up. However, recovery of parotid gland function (WSFR and scintigraphic scores) and morphology (sialographic scores) and return to the preradiation relation between WSFR and both BI/PII ratio (r = 0.75) and GR (r = −0.71) were noted in the fourth year. The differences between the nasopharyngeal and Hodgkin's lymphoma groups are attributable to the delineation of the radiation field employed in each group.  相似文献   
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