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排序方式: 共有3434条查询结果,搜索用时 156 毫秒
1.
《药学学报(英文版)》2020,10(5):799-811
Overexpression of adenosine triphosphate (ATP)-binding cassette subfamily G member 2 (ABCG2) in cancer cells is known to cause multidrug resistance (MDR), which severely limits the clinical efficacy of chemotherapy. Currently, there is no FDA-approved MDR modulator for clinical use. In this study, rociletinib (CO-1686), a mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was found to significantly improve the efficacy of ABCG2 substrate chemotherapeutic agents in the transporter-overexpressing cancer cells in vitro and in MDR tumor xenografts in nude mice, without incurring additional toxicity. Mechanistic studies revealed that in ABCG2-overexpressing cancer cells, rociletinib inhibited ABCG2-mediated drug efflux and increased intracellular accumulation of ABCG2 probe substrates. Moreover, rociletinib, inhibited the ATPase activity, and competed with [125I] iodoarylazidoprazosin (IAAP) photolabeling of ABCG2. However, ABCG2 expression at mRNA and protein levels was not altered in the ABCG2-overexpressing cells after treatment with rociletinib. In addition, rociletinib did not inhibit EGFR downstream signaling and phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Our results collectively showed that rociletinib reversed ABCG2-mediated MDR by inhibiting ABCG2 efflux function, thus increasing the cellular accumulation of the transporter substrate anticancer drugs. The findings advocated the combination use of rociletinib and other chemotherapeutic drugs in cancer patients with ABCG2-overexpressing MDR tumors. 相似文献
2.
Laura L Stafman Mary G Waldrop Adele P Williams Jamie M Aye Jerry E Stewart Elizabeth Mroczek-Musulman Karina J Yoon Kimberly Whelan Elizabeth A Beierle 《Journal of pediatric surgery》2019,54(6):1206-1213
PurposeHepatoblastoma is the most common primary liver cancer of childhood and has few prognostic indicators. We have previously shown that Proviral Integration site for Moloney murine leukemia virus (PIM3) kinase decreased hepatoblastoma tumorigenicity. We sought to determine the effect of PIM3 overexpression on hepatoblastoma cells and whether expression of PIM3 correlated with patient/tumor characteristics or survival.MethodsThe hepatoblastoma cell line, HuH6, and patient-derived xenograft, COA67, were utilized. Viability, proliferation, migration, sphere formation, and tumor growth in mice were assessed in PIM3-overexpressing cells. Immunohistochemistry was performed for PIM3 on patient samples. Correlation between stain score and clinical/pathologic characteristics was assessed.ResultsPIM3 overexpression rescued the anti-proliferative effect observed with PIM3 knockdown. Sphere formation was increased in PIM3 overexpressing cells. Cells with PIM3 overexpression yielded larger tumors than those with empty vector. Seventy-four percent of samples expressed PIM3. There was no statistical difference in patient characteristics between subjects with strong versus weak PIM3 staining, but patients with strong PIM3 staining had decreased survival.ConclusionsPIM3 expression plays a role in hepatoblastoma tumorigenesis. PIM3 was present in the majority of hepatoblastomas and higher PIM3 expression correlated with decreased survival. PIM3 warrants investigation as a therapeutic target and prognostic marker for hepatoblastoma. 相似文献
3.
Colon cancer can be treated with 5-fluorouracil (5-FU), but 5-FU resistance frequently occurs. We determined whether 5-FU resistance arises as a result of endoplasmic reticulum (ER) stress. 5-FU–resistant SNUC5 colon cancer cells (SNUC5/FUR cells) expressed higher levels of ER stress–related proteins than drug-sensitive SNUC5 cells. SNUC5/FUR cells also exhibited more intense ER staining and higher level of mitochondrial Ca2+ overload. SNUC5/FUR cells transfected with siRNA against GRP78, ATF6, ERK, or AKT were more sensitive to 5-FU than siControl RNA-transfected cells. These results suggested that 5-FU resistance was associated with ER stress in colon cancer. 相似文献
4.
Elena V. Preobrazhenskaya Aglaya G. Iyevleva Amina M. Suleymanova Vladislav I. Tiurin Natalia V. Mitiushkina Ilya V. Bizin Alexandr O. Ivanstov Olga A. Gorustovich Kseniya V. Shelekhova Denis Y. Kachanov Svetlana R. Varfolomeeva Vitaliy Y. Roschin Anna N. Kazakova Dmitriy V. Litvinov Tatiana V. Shamanskaya Nikita A. Savelov Evgeny N. Suspitsin Evgeny N. Imyanitov 《Pediatric blood & cancer》2020,67(5)
5.
《Anais brasileiros de dermatologia》2020,95(4):473-476
Vitiligo is a disease that causes macules and achromic and/or hypochromic patches, which can affect from small areas to the entire tegument. Treatment options are few and are generally ineffective. Recently, some case reports have appeared which show positive results with the use of Janus kinase inhibitors associated with phototherapy. This report details the case of a patient with rheumatoid arthritis associated with vitiligo in treatment for two years, whose condition partially improved initially after eight months of oral tofacitinib at a dose of 5 mg twice a day, without exposure to ultraviolet radiation and with continuous improvement during these two years of treatment. 相似文献
6.
【摘要】 Janus激酶信号转导和转录激活因子(JAK-STAT)信号通路在特应性皮炎(AD)免疫学通路中起着重要作用,阻断JAK-STAT信号通路的药物,如经典的JAK抑制剂托法替尼、鲁索利替尼等,已逐步应用到AD治疗的临床试验中,并取得较好的疗效。其他对JAK-STAT信号通路有抑制作用的因子,如apamin、dupilumab等也在治疗AD上显示出一定效果。本文对近年来JAK-STAT信号通路及其相关抑制剂研究进行综述。 相似文献
7.
Longer warm ischemia can accelerate tumor growth through the induction of HIF‐1α and the IL‐6–JAK–STAT3 signaling pathway in a rat hepatocellular carcinoma model 下载免费PDF全文
8.
目的:探讨白念珠菌对人急性单核细胞白血病细胞系(THP-1细胞系)分泌肿瘤坏死因子α(TNF-α)和细胞内信号分子 p38丝裂原活化蛋白激酶(MAPK)激活的影响。方法实时荧光定量 PCR 分析105、106 CFU/ml 灭活白念珠菌及阳性刺激物脂多糖刺激 THP-1细胞1、3、6 h 后 TNF-α mRNA 表达水平变化。40μg/L 地塞米松预先与 THP-1细胞共培养30 min 后,再用106 CFU/ml 白念珠菌、脂多糖刺激6 h 后检测TNF-α mRNA 表达水平。酶联免疫吸附法检测白念珠菌刺激 THP-1细胞24 h 后 TNF-α分泌量。免疫印迹法分析白念珠菌体外作用 THP-1细胞30 min、1 h 后 p38MAPK 和磷酸化 p38MAPK 的水平。结果105 CFU/ml 白念珠菌、106 CFU/ml 白念珠菌、脂多糖刺激 THP-1细胞组以及空白对照组 TNF-α mRNA 表达水平差异有统计学意义(F =110.98,P <0.001);白念珠菌刺激1、3、6 h 之间差异也有统计学意义(F =701.680,P <0.001),随培养时间延长,THP-1细胞 TNF-α mRNA 水平增高,呈时间依赖效应。106 CFU/ml 白念珠菌刺激 THP-1细胞后24 h,TNF-α蛋白水平(6385.70±533.99 ng/L)较空白对照组(147.10±0.53 ng/L)明显升高,差异有统计学意义(P <0.01)。106 CFU/ml 白念珠菌作用于 THP-1细胞30、60 min 后磷酸化 p38MAPK 蛋白水平也明显升高。40μg/L地塞米松预先与 THP-1细胞共培养30 min 后,再以106 CFU/ml 白念珠菌刺激6 h 后 TNF-α mRNA 表达水平(3.77±0.62)较未用地塞米松组(208.50±10.50)明显降低,地塞米松可阻断白念珠菌上调 TNF-α mRNA 水平。结论人 THP-1细胞体外与白念珠菌作用后激活信号分子 p38MAPK 并分泌 TNF-α,参与抗念珠菌感染固有免疫反应。 相似文献
9.
10.
Janus蛋白酪氨酸激酶是一种非受体酪氨酸激酶,参与了许多细胞因子、生长因子的信号传导,在多种细胞分化过程中发挥重要作用,与多种炎症、免疫性及肿瘤性皮肤病有关.Janus蛋白酪氨酸激酶活性的改变既可导致信号通路过度活化,也能出现信号通路失活,两种状态均能导致疾病.Janus蛋白酪氨酸激酶也是研发药物的一个重要靶点.不同的皮肤病会有不同的Janus蛋白酪氨酸激酶的异常活化,针对不同的Janus蛋白酪氨酸激酶而研发的多种抑制剂对多种皮肤病有较好的疗效. 相似文献