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排序方式: 共有262条查询结果,搜索用时 93 毫秒
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目的:探究口腔鳞癌细胞CIAP1的表达水平与临床PTP(顺铂+替尼泊甙+平阳霉素/博莱霉素)方案化疗效果及患者预后之间的关系。初步评价其表达水平是否可以指导临床个体化化疗方案的制定。方法:采用回顾性研究的方法检测了42例原发晚期口腔鳞癌标本化疗前后CIAP1的表达情况,评价其化疗前表达水平与化疗效果及临床预后之间的相关性。同时,对比分析化疗前后CIAP1的表达变化情况。结果:42例口腔鳞癌标本中CIAP1在胞质及胞核均有不同程度的表达,其胞质表达水平与化疗效果及预后显著相关。化疗前后口腔鳞癌标本中CIAP1的表达没有相关性。结论:胞质CIAP1表达水平是临床PTP方案化疗疗效及患者预后的一个有效预测因子。 相似文献
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Somatostatin is a peptide with a potent and broad antisecretory action, which makes it an invaluable drug target for the pharmacological management of pituitary adenomas and neuroendocrine tumors. Somatostatin receptors (SSTR1, 2A and B, 3, 4 and 5) belong to the G protein coupled receptor family and have a wide expression pattern in both normal tissues and solid tumors. Investigating the function of each SSTR in several tumor types has provided a wealth of information about the common but also distinct signaling cascades that suppress tumor cell proliferation, survival and angiogenesis. This provided the rationale for developing multireceptor-targeted somatostatin analogs and combination therapies with signaling-targeted agents such as inhibitors of the mammalian (or mechanistic) target of rapamycin (mTOR). The ability of SSTR to internalize and the development of rabiolabeled somatostatin analogs have improved the diagnosis and treatment of neuroendocrine tumors. 相似文献
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Evaluation of oral pharmacokinetics,in vitro metabolism,blood partitioning and plasma protein binding of novel antidiabetic agent,S009‐0629 in rats 下载免费PDF全文
《Drug development research》2018,79(4):173-183
S009‐0629 [methyl‐8‐(methylthio)‐2‐phenyl‐6‐p‐tolyl‐4,5‐dihydro‐2H‐benzo[e]indazole‐9‐carboxylate] is a novel antidiabetic agent with PTP1B inhibitory activity. In this study, we have investigated the in vitro metabolic stability, plasma protein binding, blood partitioning, and oral pharmacokinetic study of S009‐0629 in rats. The plasma protein binding, blood partitioning, and metabolic stability were determined by HPLC method. The oral pharmacokinetic study was analyzed by liquid chromatography coupled mass spectrometry (LC‐MS/MS) method. The plasma protein binding of S009‐0629 using modified charcoal adsorption method at 5 and 10 µg/mL was 80.58 ± 1.04% and 81.95 ± 1.15%, respectively. The KRBC/PL of S009‐0629 was independent of concentration and time. The in‐vitro half‐life of S009‐0629 at 5 and 10 µM using rat liver microsomes was determined as 273 ± 24.46 and 281.67 ± 26.53 min, respectively. After oral administration, S009‐0629 exhibited Cmax 55.51 ± 1.18 ng/mL was observed at 18 hr (tmax). S009‐0629 was found to have the large apparent volume of distribution (1,894.93 ± 363.67 L/kg). Oral in‐vivo t1/2 of S009‐0629 was found to be 41.23 ± 5.96 hr. A rapid and highly sensitive LC‐MS/MS method was validated for S009‐0629 in rat plasma. S009‐0629 has high plasma protein binding and low hepatic extraction. S009‐0629 has no affinity with human P‐gp and BCRP in ATPase assay. After oral dosing, S009‐0629 has slow absorption and elimination in rats. 相似文献
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《Journal of pharmacological sciences》2014,124(2):276-286
The pharmacological profile of (S)-7-(2-{2-[(E)-2-cyclopentylvinyl]-5-methyloxazol-4-yl}-ethoxy)-2-[(2E,4E)-hexadienoyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (KY-201), a peroxisome proliferator-activated receptor (PPAR) γ agonist, was compared with that of rosiglitazone in ovariectomized rats. The serum triglyceride and non-esterified fatty acid reducing effects of KY-201 at 3 and 10 mg/kg per day for 6 weeks were similar to those of rosiglitazone despite its weaker PPARγ agonistic activity. KY-201 had no effects on body weight gain, blood volume, or heart and adipose weights, while rosiglitazone at 10 mg/kg per day increased them. KY-201 had few effects on bone mineral density (BMD) or fat in marrow (FM), whereas rosiglitazone strongly decreased BMD and increased FM. The PPARγ agonistic activity of KY-201 was weaker than that of rosiglitazone in ST-2 cells, and KY-201 reduced osteoblast differentiation and increased adipocyte differentiation less potently than rosiglitazone in rat bone marrow-derived mesenchymal stem cells. KY-201, but not rosiglitazone inhibited protein tyrosine phosphatase 1B (PTP1B) and increased phosphorylation of the insulin receptor in HepG2 cells. These results suggest that the hypolipidemic effects of KY-201 are similar to those of rosiglitazone, but with less adverse effects, due to the combination of PPARγ partial activation and PTP1B inhibition. KY-201 would be useful for treatments of diabetic patients at high risk of osteoporosis, cardiovascular disease, and/or obesity. 相似文献
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Long-term potentiation (LTP) observed at the synapses of mossy fiber-CA3(MF-CA3) pathway differs from that observed at the Schaffer collateral-CA1 pathway (SC-CA1), in being independent of N-methyl-D-aspartate (NMDA) receptors. The induction and expression mechanisms of MF-CA3 LTP remain to be determined. We have compared the occurrence and magnitude of LTP with that of two other indicators of presynaptic plasticity, post-tetanic potentiation (PTP) and paired-pulse facilitation in control brain slices from young rats and in slices treated with phorbol-12, 13-diacetate (PDAc), a protein kinase C activator. Paired-pulse facilitation is a potentiation of the second of two responses at intervals of tens of milliseconds and is due to a presynaptic calcium increase. Tetanic stimulation of mossy fibers induced LTP is area CA3 in only 64% of slices. In those slices that showed LTP, the size of the PIP was significantly greater than in those slices that did not, and the degree of correlation between LTP and PTP amplitude overall was r = 0.7. The degree of paired-pulse facilitation before tetanic stimulation was also positively correlated to the occurrence and magnitude of LTP and PTP after tetanic stimulation. The correlation coefficient between PTP and PPF was 0.749 for all slices studied, while that between LTP and PPF was 0.835 overall. Application of PDAc potentiated synaptic transmission and abolished paired-pulse facilitation (control ratio of second to first response, 2.1; after PDAc ratio 0.8) and LTP. PTP was absent at the control stimulus intensity in PDAc, but was apparent if the stimulus intensity was reduced to give a response of the same amplitude as before administration of PDAc. Stable LTP was also accompanied by a marked decrease in paired-pulse facilitation. These data suggest that MF-CA3 LTP, PTP and paired-pulse facilitation share common mechanisms and are all at least primarily of presynaptic origin. The occurrence of large paired-pulse facilitation or PTP is a predictor of a preparation which will show LTP. It is likely that presynaptic [Ca2-], is an essential factor in LTP, PTP and paired-pulse facilitation, as well as the potentiation induced by application of PDAc, but the factors which determine whether or not [Ca2-], rises following these various stimuli are not clear from the techniques used in these investigations. © 1996 Wiley-Liss, Inc. 相似文献
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《中国中药杂志》2009,34(12)
目的:通过化学法合成具有PTP1 B酶抑制活性的新型溴酚衍生物-(2'-溴4',5'-二甲氧基-苯基)-(2,3-二溴-4,5-二甲氧基-苯基)-甲烷.方法:采用傅克酰基化、逐级溴化、脱羰基等经典合成反应合成目标化合物6.采用EI-Ms,HREI-MS,~(1)H-NMR,~(13)C-NMR,IR等方法对合成中间体及目标化合物进行结构鉴定.通过比色法对化合物6进行PTP1 B酶抑制活性测试.结果:采用四步法成功合成了目标化合物6,体外活性测试结果表明其具有一定的PTP1 B酶抑制活性.结论:采用化学法合成了目标化合物6,总产率为20%,该化合物为新化合物,具有一定的PTP1 B酶抑制活性5 mg·L~(-1),酶抑制率为40.16%. 相似文献
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荞麦花叶黄酮对2型糖尿病大鼠胰岛素抵抗及肝组织PTP1B的影响 总被引:1,自引:0,他引:1
目的:探讨荞麦花叶黄酮(FBFL)对2型糖尿病大鼠降血糖、改善胰岛素抵抗的作用及其机制.方法:雄性健康Wistar大鼠70只,随机抽取10只作为正常对照组,其余60只大鼠每天灌胃脂肪乳,第14天开始腹腔注射小剂量四氧嘧啶,隔日1次,共3次,同时继续灌胃脂肪乳.末次腹腔注射四氧嘧啶72 h后,用血糖仪测定空腹血糖和用K_(IPT)值判定胰岛素抵抗性.K_(IPT)<正常组的60%作为2型糖尿病胰岛素抵抗大鼠.将成模大鼠随机分为模型组,阳性药物组,FBFL低、中、高剂量组,连续4周.末次给药后禁食,用血糖仪测空腹血糖(FBG),用正糖钳技术判定胰岛素抵抗性,用生化分析仪测定游离脂肪酸(FFA),放免法测定血浆胰岛素(INS),免疫组织化学法检测肝组织蛋白酪氨酸磷酸酶1B(PTP1B)表达.结果:与正常组比较,模型组大鼠FBG,INS,FFA含量明显升高(P<0.135,P<0.01);大鼠葡萄糖输注速率(GIR)明显下降;肝组织PTP1B表达增加.各剂量FBFL能不同程度的改善上述指标的变化,明显改善胰岛素抵抗性,增加胰岛素敏感性,使肝组织PTP1B表达下调,并呈一定剂量依赖性.结论:FBFL对四氧嘧啶加脂肪乳所致2型糖尿病大鼠胰岛素抵抗具有明显的改善作用,并呈一定剂量依赖性. 相似文献
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核因子(NF)-κB是Rel转换因子家族的成员,正常情况下与细胞内抑制剂IκB-α形成复合物,细胞受刺激后NF-κB出与IκB-α复合物解离,NF-κB转移到细胞内,以调节基因的转录诱导细胞凋亡。细胞色素-C是由于线粒体呼吸频率增加,通透性转移孔(PTP)开放,由线粒体膜释放出来,然后细胞色素C激活caspase的连锁反应,导致细胞凋亡。 相似文献