全文获取类型
收费全文 | 143篇 |
免费 | 4篇 |
专业分类
儿科学 | 9篇 |
妇产科学 | 1篇 |
基础医学 | 4篇 |
临床医学 | 13篇 |
内科学 | 31篇 |
神经病学 | 3篇 |
外国民族医学 | 1篇 |
综合类 | 16篇 |
预防医学 | 1篇 |
眼科学 | 2篇 |
药学 | 22篇 |
中国医学 | 2篇 |
肿瘤学 | 42篇 |
出版年
2023年 | 1篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2017年 | 1篇 |
2015年 | 2篇 |
2014年 | 1篇 |
2013年 | 7篇 |
2012年 | 6篇 |
2011年 | 6篇 |
2010年 | 10篇 |
2009年 | 7篇 |
2008年 | 8篇 |
2007年 | 12篇 |
2006年 | 4篇 |
2005年 | 4篇 |
2004年 | 7篇 |
2003年 | 2篇 |
2002年 | 5篇 |
2001年 | 4篇 |
2000年 | 4篇 |
1998年 | 4篇 |
1997年 | 5篇 |
1996年 | 5篇 |
1995年 | 1篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1992年 | 5篇 |
1990年 | 6篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1981年 | 1篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 1篇 |
排序方式: 共有147条查询结果,搜索用时 15 毫秒
141.
We investigated the effects of the autophagy inhibitor hydroxychloroquine (HCQ) on cell death of cytosine arabinoside (Ara-C)-resistant human acute myeloid leukemia (AML) cells. Ara-C-sensitive (U937, AML-2) and Ara-C-resistant (U937/AR, AML-2/AR) human AML cell lines were used to evaluate HCQ-regulated cytotoxicity, autophagy, and apoptosis as well as effects on cell death-related signaling pathways. We found that HCQ-induced dose- and time-dependent cell death in Ara-C-resistant cells compared to Ara-C-sensitive cell lines. The extent of cell death and features of HCQ-induced autophagic markers including increase in microtubule-associated protein light chain 3 (LC3) I conversion to LC3-II, beclin-1, ATG5, as well as green fluorescent protein-LC3 positive puncta and autophagosome were remarkably greater in U937/AR cells. Also, p62/SQSTM1 was increased in response to HCQ. p62/SQSTM1 protein interacts with both LC3-II and ubiquitin protein and is degraded in autophagosomes. Therefore, a reduction of p62/SQSTM1 indicates increased autophagic degradation, whereas an increase of p62/SQSTM1 by HCQ indicates inhibited autophagic degradation. Knock down of p62/SQSTM1 using siRNA were prevented the HCQ-induced LC3-II protein level as well as significantly reduced the HCQ-induced cell death in U937/AR cells. Also, apoptotic cell death and caspase activation in U937/AR cells were increased by HCQ, provided evidence that HCQ-induced autophagy blockade. Taken together, our data show that HCQ-induced apoptotic cell death in Ara-C-resistant AML cells through autophagy regulation. 相似文献
142.
目的 探讨阿糖胞苷(Ara-C)通过自噬途径影响人红白血病K562细胞株增殖、凋亡的作用及可能的机制.方法 采用CCK-8法检测不同浓度的Ara-C作用24 h和48 h后细胞增殖抑制率;流式细胞术(FCM)检测凋亡率和周期;Hoechest染色观察细胞核染色质的形态,吖啶橙染色观察细胞酸性自噬小泡;Western blot检测p38和p-p38蛋白表达变化;RT-PCR和免疫荧光检测自噬凋亡相关基因和蛋白的表达水平.结果 CCK-8检测发现不同浓度的Ara-C均能抑制K562细胞增殖,并呈浓度和时间依赖性;FCM检测显示Ara-C能增加细胞的凋亡和将细胞周期阻滞在S期;Hoechest染色发现Ara-C处理K562细胞后呈凋亡形态改变;吖啶橙染色发现Ara-C组细胞绿色荧光增强,细胞出现大量的酸性自噬小泡;RT-PCR检测发现Ara-C上调自噬关键基因Beclin-1、LC3A和LC3B表达;Western blot检测发现Ara-C增加磷酸化p38表达;免疫荧光检测发现Ara-C增加LC3表达.结论 Ara-C能够激活p-p38介导的K562细胞发生自噬,进而抑制细胞增殖和促进细胞凋亡作用. 相似文献
143.
Corsetti MT Salvi F Perticone S Baraldi A De Paoli L Gatto S Pietrasanta D Pini M Primon V Zallio F Tonso A Alvaro MG Ciravegna G Levis A 《Leukemia research》2011,35(8):991-997
The histone deacetylase inhibitor (HDACi) valproic acid (VPA) has been shown to be active on acute myeloid leukemia (AML) and refractory anemia with excess of blasts (RAEB). Thirty-one elderly AML/RAEB patients (AML n = 25; RAEB n = 6) with a high rate of comorbidity were entered in a phase II study with low-dose cytarabine (Ara-C) and VPA. Fitness was evaluated by means of the Comprehensive Geriatric Assessment (CGA), including the Cumulative Illness Rating Scale (CIRS) score, the self-sufficiency scores of Activity of Daily Living (ADL) and Instrumental Activity of Daily Living (IADL). Eight patients obtained a lasting complete remission and 3 other patients obtained hematologic improvement for a total response rate of 35%. Five of 11 responding patients were relapsed or resistant after a previous treatment with Ara-C. Seven of 11 responding patients were assessed as frail at enrolment and/or had IADL impairment. Grades 3 and 4 toxicities were mainly hematological. Low-dose Ara-C and VPA is a relatively non-toxic combination with good therapeutic activity in elderly patients with AML/RAEB. This therapeutic approach represents an alternative treatment for patients who cannot undergo standard induction therapy. 相似文献
144.
本研究探讨Wnt3a基因修饰对小鼠骨髓间充质干细胞(MSC)抗阿糖胞苷损伤的作用.通过重组腺病毒系统感染小鼠MSC,建立能够稳定高效表达Wnt3a基因的基因修饰MSC;在体外培养体系中加入不同浓度的阿糖胞分别诱导对基因修饰MSC与未经基因修饰MSC的损伤,设置对应的对照,通过CCK-8法、流式细胞术检测MSC的生长增殖以及凋亡情况;用Western blot测定MSC中与细胞凋亡有关的BCL-2蛋白的表达水平.结果表明,阿糖胞苷对基因修饰MSC的增殖抑制程度较未经基因修饰MSC明显减低,差异有统计学意义(p<0.05);去除阿糖胞苷后,基因修饰MSC的增殖生长能力在72小时后就开始恢复,而未经基因修饰MSC的增殖生长能力在72小时后仍然被抑制.在凋亡方面,阿糖胞苷诱导的基因修饰MSC的凋亡率明显降低(p<0.05),与未经基因修饰MSC相比,基因修饰MSC中BCL-2蛋白的表达上调(p<0.05).结论:Wnt3a基因修饰能明显减轻阿糖胞苷对小鼠骨髓MSC的损伤作用. 相似文献
145.
The subventricular zone (SVZ) is a dynamic cellular niche with unique neurogenic properties that are, as of yet, not fully understood. Astrocytes residing in the SVZ have been shown to spawn migratory neuroblasts via transitory amplifying progenitor cells. These migratory neuroblasts play a role in maintaining the olfactory circuitry in healthy brains and potentially have restorative properties after brain injury. Therefore, it is imperative to understand the basic nature of these neurogenic astrocytes in order to gain a more cohesive picture of SVZ adult neurogenesis. However, one of the obstacles in this line of research is to specifically genetically modify SVZ astrocytes. Viral vector systems, based on adeno-associated viruses and lentiviruses, are flexible gene transfer systems that allow long-term transgene expression in a host cell. Electroporation allows for the transient expression of larger transgenes; whereas the cre/loxP system provides a lifetime of inherently stable genetic modulation. The benefits and drawbacks of these transduction methods and the application of various astrocyte-specific promoters are discussed with regard to their efficiency and accuracy when transducing adult SVZ astrocytes in the mouse brain. In vivo studies that manipulate gene expression in SVZ astrocytes will be essential to fully dissect and understand the complex molecular and cellular properties of the SVZ in the upcoming years. 相似文献
146.
147.
Shunsuke Yui Satoshi Wakita Yasunobu Nagata Yasuko Kuribayashi Toshio Asayama Yusuke Fujiwara Masahiro Sakaguchi Satoshi Yamanaka Atsushi Marumo Ikuko Omori Ryosuke Kinoshita Daishi Onai Mika Sunakawa Yuta Kaito Kazuki Inai Taichiro Tokura Atsushi Takeyoshi Shunichi Yasuda Shunsuke Honma Kazutaka Nakayama Tsuneaki Hirakawa Kunihito Arai Tomoaki Kitano Muneo Okamoto Koiti Inokuchi Hiroki Yamaguchi 《Asia-Pacific Journal of Clinical Oncology》2023,19(1):136-148