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1.
Neoadjuvant Therapy with Drug Arglabin for Breast Cancer with Expression of H-Ras Oncoproteins 下载免费PDF全文
Sergazy AdekenovAinur Zhumakayeva Vladimir PerminovBakhytzhan BekmanovKayrolla Rakhimov 《Asian Pacific journal of cancer prevention》2020,21(11):3441-3447
Backgrounds: In breast cancer, blocking of Ras signaling and inhibition of H-Ras is quite promising. H-Ras may become a target for farnesyl transferase inhibitors, and in combination with other immunohistochemical factors it will contribute to the progression of a breast tumor. Purpose: The aim of this study was to evaluate the effectiveness of neoadjuvant therapy for breast cancer with the inclusion of farnesyl transferase inhibitor, arglabin interfering with the expression and concentration of H-Ras oncoproteins. Methods: Depending on the presence of H-Ras oncoproteins after Western-blot hybridization, the patients were divided a negative and positive expression of H-Ras groups. Results: Correlation analysis of methods used for determining the expression ability and concentration of H-Ras oncoproteins (immunohistochemistry and Western-blot analysis) demonstrated substantial statistical relationship Rs=0.71, p=0.03. The H-Ras oncoproteins were absent in patients receiving either “Arglabin” or standard AC regimen. However, in the AC + Arglabin group, there was a varying degrees of positive concentration of H-Ras oncoproteins (Kruskal-Wallis=6.92; p=0.03). Conclusion: These results indicate that Arglabin attenuates H-Ras oncoproteins expression which is a promising therapeutic target for breast cancer. 相似文献
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《Drug metabolism and pharmacokinetics》2020,35(4):368-373
A recent report demonstrated that sesamin strongly and non-competitively inhibits S-warfarin 7-hydroxylation activity in human liver microsomes with a Ki value of 0.2 μM. This finding suggests that sesamin predominantly binds to CYP2C9 at another site for which it has a higher affinity than its affinity for the active site, thereby inhibiting the activity of CYP2C9 non-competitively. In this study, we found that sesamin competitively inhibited the 7-hydroxylation activity of S-warfarin in human liver microsomes with a Ki value of 15.7 μM. In addition, the recombinant CYP2C9-dependent 7-hydroxylation activity of S-warfarin was competitively inhibited by sesamin with a Ki value of 13.1 μM. These results are consistent with the fact that sesamin is a good substrate of CYP2C9, and its activity follows Michaelis-Menten kinetics. As the plasma concentration of sesamin after its administration is usually lower than 0.01 μM, the inhibition of S-warfarin metabolism by sesamin does not appear to be severe. 相似文献
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目的 目的 探讨CD4+
CD25+
调节性T细胞 (Tregs) 对日本血吸虫病疫苗保护性效果的影响及其机制。 方法 方法 雌性
BALB/c小鼠随机分成5组, 即正常对照组、 感染对照组、 抗CD25单克隆抗体 (anti?CD25 mAb) 组、 谷胱甘肽?S?转移酶
(Gluthatione?S?transferase,GST) 免疫组和GST/anti?CD25 mAb联合组。分别在感染后2、 3、 4、 5周剖杀小鼠, 收集脾细胞
及培养上清, 采用流式细胞术检测脾细胞中CD4+
CD25+
Tregs比例, 双抗夹心ELISA法测定脾细胞培养上清中的IFN?γ、
IL?2、 IL?4、 IL?5和TGF?β水平。感染后5周杀鼠, 门静脉冲虫, 统计每只小鼠虫荷及每克肝脏虫卵数; 肝组织石蜡切片HE
染色观察虫卵肉芽肿病理变化。 结果 结果 感染后5周, GST免疫组小鼠减虫率为24.98%, 而GST/anti?CD25 mAb联合组减
虫率达43.13%; GST免疫组小鼠脾细胞中CD4+
CD25+
Foxp3+
比例显著高于感染对照组 (P < 0.05), 而anti?CD25 mAb组小
鼠脾细胞中CD4+
CD25+
Foxp3+
比例显著低于感染对照组 (P < 0.01)。使用anti?CD25 mAb后2周, GST/anti?CD25 mAb联合
组小鼠脾细胞培养上清中IL?4、 IL?5、 IFN?γ和IL?2含量均较其他组高; 各组小鼠肝脏病理变化和脾细胞培养上清中TGF?
β水平间差异均无统计学意义 (P 均 > 0.05)。结论 结论 GST疫苗可引起日本血吸虫感染宿主CD4+
CD25+
Tregs 明显上升, 从
而导致其保护性效果欠佳; anti?CD25 mAb部分封闭CD4+
CD25+
Tregs后有利于增强日本血吸虫病疫苗的免疫保护性效
果, 其机制可能与Th1、 Th2型免疫反应增强有关。 相似文献
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口腔鳞癌P-gp、GST-π表达与化疗药物耐受性 总被引:1,自引:1,他引:1
目的 探讨P-糖蛋白(P-glycoprotein,P-gp)和谷胱甘肽S转移酶π(glutathione transferase-π,GST-π)表达与化疗药物耐受性的关系。方法 采用免疫组化过氧化物酶标记法检测口腔颌面部鳞癌和正常口腔粘膜组织样本中P-gp和GST-π的表达,结合MTT药敏检测结果分析。结果 P-gp和GST-π在恶性肿瘤中阳性表达率分别为57.1%和53.6%,在正常组织中未见表达;P-gp的表达与化疗药物总体耐受性有关;GST-π的表达与患者顺铂耐受性有关。结论 P-gp和GST-π的阳性表达提示患者有化疗药物耐受倾向。P-pg和GST-π检测对判断口腔颌面部恶性肿瘤化疗耐药性有指导意义。 相似文献
9.
Junhong Zhang Ni Wang Yuanyuan Zhou Kaili Wang Yaxin Sun Hao Yan Wenchao Han Xinying Wang Bo Wei Yu Ke Xia Xu 《Phytotherapy research : PTR》2021,35(1):494-503
Oridonin (Ori) is a natural tetracyclic diterpenoid active compound with excellent antitumor activity, but the mechanism of Ori on esophageal cancer cell, TE1, remains unclear. In this study, we examined the levels of intracellular iron, malondialdehyde, and reactive oxygen species after Ori treatment, while interfering with the effects of Ori with ferroptosis inhibitor, demonstrating that Ori's inhibition of TE1 cell proliferation is associated with ferroptosis. To understand the molecular mechanism of Ori, we performed UPLC–MS/MS metabolomics profiling on TE1 cells, which show that gamma‐glutamyl amino acids (gamma‐glutamylleucine, gamma‐glutamylvaline), 5‐oxoproline, glutamate, GSH, and GSSG are changed significantly after Ori treatment. Meanwhile, the activity of gamma‐glutamyl transpeptidase 1 (GGT1) decreased. This revealed that Ori inhibited the gamma‐glutamyl cycle in TE1 cells. Furthermore, we found that Ori can covalently bind to cysteine to form the conjugate oridonin‐cysteine (Ori‐Cys), resulting in the inhibition of glutathione synthesis, which is consistent with the decrease in the enzymatic activity of glutamate cysteine ligase catalytic subunit (GCLC). Eventually, the value of intracellular GSH/GSSG was reduced, and the enzymatic activity of the glutathione peroxidase 4 (GPX4) was significantly decreased. In conclusion, our experiments indicated that Ori can inhibit the gamma‐glutamyl cycle, thereby inducing ferroptosis to exert anti‐cancer activity. 相似文献
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