全文获取类型
收费全文 | 4454篇 |
免费 | 557篇 |
国内免费 | 170篇 |
专业分类
耳鼻咽喉 | 12篇 |
儿科学 | 51篇 |
妇产科学 | 51篇 |
基础医学 | 715篇 |
口腔科学 | 54篇 |
临床医学 | 234篇 |
内科学 | 538篇 |
皮肤病学 | 67篇 |
神经病学 | 251篇 |
特种医学 | 34篇 |
外国民族医学 | 1篇 |
外科学 | 247篇 |
综合类 | 461篇 |
现状与发展 | 2篇 |
预防医学 | 101篇 |
眼科学 | 40篇 |
药学 | 1035篇 |
中国医学 | 390篇 |
肿瘤学 | 897篇 |
出版年
2024年 | 18篇 |
2023年 | 134篇 |
2022年 | 193篇 |
2021年 | 303篇 |
2020年 | 276篇 |
2019年 | 236篇 |
2018年 | 231篇 |
2017年 | 220篇 |
2016年 | 214篇 |
2015年 | 263篇 |
2014年 | 393篇 |
2013年 | 397篇 |
2012年 | 338篇 |
2011年 | 385篇 |
2010年 | 302篇 |
2009年 | 255篇 |
2008年 | 221篇 |
2007年 | 155篇 |
2006年 | 154篇 |
2005年 | 121篇 |
2004年 | 108篇 |
2003年 | 78篇 |
2002年 | 42篇 |
2001年 | 21篇 |
2000年 | 25篇 |
1999年 | 6篇 |
1998年 | 7篇 |
1997年 | 6篇 |
1996年 | 3篇 |
1995年 | 5篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1991年 | 5篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1987年 | 2篇 |
1985年 | 9篇 |
1984年 | 6篇 |
1983年 | 6篇 |
1982年 | 7篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1979年 | 5篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1974年 | 1篇 |
排序方式: 共有5181条查询结果,搜索用时 203 毫秒
991.
Baolei Zhao Yong Ma Zhilin Xu Jizhou Wang Fengjun Wang Dawei Wang Shangha Pan Yaohua Wu Huayang Pan Dongsheng Xu Lianxin Liu Hongchi Jiang 《Cancer letters》2014
The present study aimed to investigate the anti-cancer effects of hydroxytyrosol (HT) in human hepatocellular carcinoma (HCC) cells. Our results show that HT could inhibit proliferation, induce G2/M cell cycle arrest and apoptosis in human HCC cells. Mechanically, we found that HT could suppress the activation of AKT and nuclear factor-kappa B (NF-κB) pathways. HT also significantly inhibited the tumor growth, angiogenesis and the activation of AKT and NF-κB pathways in an orthotopic model of human HCC in vivo. These data suggest that HT may be a promising candidate agent for the treatment of HCC. 相似文献
992.
Despite tremendous advances in the targeted therapy for various types of hematological malignancies with successful improvements in the survival rates, emerging resistance issues are startlingly high and novel therapeutic strategies are urgently needed. In addition, chemoprevention is currently becoming an elusive goal. Plant-derived natural products have garnered considerable attention in recent years due to the potential dual functions as chemotherapeutics and dietary chemoprevention. One of the particularly ubiquitous families is the polyphenolic flavonoids. Among them, baicalin and its aglycone baicalein have been widely investigated in hematological malignancies because both of them exhibit remarkable pharmacological properties. This review focuses on the recent achievements in drug discovery research associated with baicalin and baicalein for hematological malignancy therapies. The promising anticancer activities of these two flavonoids targeting diverse signaling pathways and their potential biological mechanisms in different types of hematological malignancies, as well as the combination strategy with baicalin or baicalein as chemotherapeutic adjuvants for recent therapies in these intractable diseases are discussed. Meanwhile, the biotransformation of baicalin and baicalein and the relevant approaches to improve their bioavailability are also summarized. 相似文献
993.
Background
Human epidermal growth factor receptor 2 (HER2) is overexpresed in 15–20% of all breast cancers. Treatment with trastuzumab has led to an improved outcome and prolonged survival of HER2-positive breast cancer patients and today the drug is established as standard of care in both the adjuvant and metastatic settings. However, trastuzumab resistance is common and a major focus in the treatment of HER2-positive breast cancer has been developing therapeutic agents to either potentiate the effect of trastuzumab or to target cells which have become resistant to trastuzumab. The present review addresses efficacy and toxicity of dual targeting in HER2-positive breast cancer.Materials and methods
A computer-based literature search was carried out using PubMed; data reported at international meetings and clinicaltrials.gov was included.Results
This paper describes efficacy and safety of lapatinib, pertuzumab or trastuzumab-DM1 in combination with trastuzumab in the (neo)adjuvant and metastatic settings. Furthermore, combinations of trastuzumab and drugs targeting the downstream pathway are described.Conclusion
Dual blockade is likely to represent a substantial advance for patients with HER2-positive breast cancer. However, the relevant subpopulation remains to be defined and side effects including cardiotoxicity might be a limiting factor to the use. There is an urgent need for prospective biomarker-driven trials to identify patients for whom dual targeting is cost-effective. 相似文献994.
Approximately 70−75% of breast cancers express the estrogen receptor (ER), indicating a level of dependence on estrogen for growth. Endocrine therapy is an important class of target-directed therapy that blocks the growth-promoting effects of estrogen via ER. Although endocrine therapy continues to be the cornerstone of effective treatment of ER-positive (ER+) breast cancer, many patients with advanced ER+ breast cancer encounter de novo or acquired resistance and require more aggressive treatment such as chemotherapy. Novel approaches are needed to augment the benefit of existing endocrine therapies by prolonging time to disease progression, preventing or overcoming resistance, and delaying the use of chemotherapy. 相似文献
995.
996.
Hoechst33342/PI双染法和TUNEL染色技术检测神经细胞凋亡的对比研究 总被引:1,自引:0,他引:1
目的: 利用Hoechst33342/PI双染法和原位末端标记法(TUNEL)染色检测纳米二氧化硅(nm-SiO2)对神经细胞凋亡的影响,比较两种检测方法的优缺点。方法:以体外培养的人神经母细胞瘤SK-N-SH为研究对象,15和30 nm粒径的nm-SiO2(剂量为2.5、5、10 μg/mL)分别处理细胞24 h,另设1~5 μm SiO2组和溶剂对照组,采用Hoechst33342/PI双染法和TUNEL染色检测各处理组对SK-N-SH细胞凋亡的影响。结果:与对照组相比,两种检测方法分析均显示了nm-SiO2处理组SK-N-SH细胞凋亡率显著增加(P<0.05),且具有尺寸、剂量依赖性,而微米级SiO2对凋亡的影响不显著(P>0.05)。结论:nm-SiO2能诱导SK-N-SH细胞凋亡。Hoechst33342/PI双染法特异性高,简单易行;TUNEL法灵敏度高,能检测少量的细胞凋亡,但成本较高,两种方法可结合使用以便更加准确的检测神经细胞的凋亡。 相似文献
997.
998.
V D'Amato R Rosa C D'Amato L Formisano R Marciano L Nappi L Raimondo C Di Mauro A Servetto C Fusciello B M Veneziani S De Placido R Bianco 《British journal of cancer》2014,110(12):2887-2895
Background:
Cetuximab is the only targeted agent approved for the treatment of head and neck squamous cell carcinomas (HNSCC), but low response rates and disease progression are frequently reported. As the phosphoinositide 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) pathways have an important role in the pathogenesis of HNSCC, we investigated their involvement in cetuximab resistance.Methods:
Different human squamous cancer cell lines sensitive or resistant to cetuximab were tested for the dual PI3K/mTOR inhibitor PF-05212384 (PKI-587), alone and in combination, both in vitro and in vivo.Results:
Treatment with PKI-587 enhances sensitivity to cetuximab in vitro, even in the condition of epidermal growth factor receptor (EGFR) resistance. The combination of the two drugs inhibits cells survival, impairs the activation of signalling pathways and induces apoptosis. Interestingly, although significant inhibition of proliferation is observed in all cell lines treated with PKI-587 in combination with cetuximab, activation of apoptosis is evident in sensitive but not in resistant cell lines, in which autophagy is pre-eminent. In nude mice xenografted with resistant Kyse30 cells, the combined treatment significantly reduces tumour growth and prolongs mice survival.Conclusions:
Phosphoinositide 3-kinase/mammalian target of rapamycin inhibition has an important role in the rescue of cetuximab resistance. Different mechanisms of cell death are induced by combined treatment depending on basal anti-EGFR responsiveness. 相似文献999.
The activation of the PI3K/AKT/m TOR pathway plays a key role in ovarian cancer tumorigenesis, progression and chemotherapy resistance. This study aimed to explore the possible mechanism that PI-103, a dual inhibitor of phosphatidylinositide 3-kinase and m TOR, enhances the sensitivity of SKOV3/DDP ovarian cancer cell line to cisplatin chemotherapy. The results showed that PI-103 could significantly increase the sensitivity of SKVO3/DDP cells to cisplatin through inhibiting the activation of PI3K/Akt/m TOR signaling pathway and inducing cell cycle arrest and apoptosis. 相似文献
1000.
目的探讨磷脂酰肌醇3激酶/蛋白激酶B1/哺乳动物雷帕霉素靶蛋白(PI3K/Akt1/m TOR)通路与表皮生长因子受体(EGFR)基因的关系,及其PI3K/Akt1/m TOR通路导致EGFR-酪氨酸激酶抑制剂(TKI)耐药的具体机制。方法选择135例未经过放化疗或靶向药物治疗的非小细胞肺癌(NSCLC)患者的肿瘤组织标本,检测其EGFR、PIK3CA、Akt1和m TOR的mRNA表达水平,并进行相关性分析。结果 EGFR与Akt1、m TOR的表达水平呈正相关(r分别为0.342、0.320和0.281,均P<0.01),与PIK3CA基因无关。结论 EGFR基因表达与Akt1和m TOR相关,与PIK3CA无关,提示EGFR基因可能直接激活Akt及其下游通路,而不经过PI3K。 相似文献