全文获取类型
收费全文 | 317篇 |
免费 | 20篇 |
国内免费 | 4篇 |
专业分类
儿科学 | 2篇 |
妇产科学 | 1篇 |
基础医学 | 29篇 |
临床医学 | 40篇 |
内科学 | 100篇 |
特种医学 | 1篇 |
外科学 | 1篇 |
综合类 | 19篇 |
预防医学 | 2篇 |
药学 | 28篇 |
中国医学 | 1篇 |
肿瘤学 | 117篇 |
出版年
2024年 | 1篇 |
2023年 | 4篇 |
2022年 | 6篇 |
2021年 | 20篇 |
2020年 | 20篇 |
2019年 | 11篇 |
2018年 | 6篇 |
2017年 | 17篇 |
2016年 | 13篇 |
2015年 | 14篇 |
2014年 | 29篇 |
2013年 | 36篇 |
2012年 | 16篇 |
2011年 | 25篇 |
2010年 | 13篇 |
2009年 | 20篇 |
2008年 | 11篇 |
2007年 | 7篇 |
2006年 | 9篇 |
2005年 | 6篇 |
2004年 | 8篇 |
2003年 | 4篇 |
2002年 | 5篇 |
2001年 | 7篇 |
2000年 | 1篇 |
1999年 | 8篇 |
1998年 | 11篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 5篇 |
1994年 | 3篇 |
1993年 | 1篇 |
排序方式: 共有341条查询结果,搜索用时 218 毫秒
61.
目的 研究尼洛替尼(nilotinib,AMN107诱导K562/A02细胞凋亡及对血红素加氧酶-1(HO-1基因表达的影响。方法 采用荧光原位杂交(FISH法检测K562/A02细胞中的BCR-ABL融合基因;用不同浓度的AMN107分别处理K562/A02细胞24 h后,通过实时荧光定量PCR(RQ-PCR法检测BCR-ABL融合基因mRNA的表达水平;采用MTT法观察细胞增殖变化;通过Annexin V/PI双染色法检测细胞凋亡和细胞周期;采用RT-PCR法和Western Blot法检测HO-1基因的表达。 结果 FISH法分析结果显示,K562/A02细胞BCR-ABL融合基因阳性细胞占细胞总数98%;RQ-PCR法检测结果显示,0,5,10,20 μmol·L-1 AMN107作用于K562/A02细胞24 h后BCR-ABL融合基因表达随AMN107浓度增加而逐渐下降;MTT法和Annexin V/PI法显示与对照组相比,细胞存活率随AMN107浓度升高而下降,凋亡率逐渐增加;细胞周期分析显示,经AMN107处理的细胞,G0/G1期和S期细胞明显减少,细胞阻滞在G2/M期;RT-PCR法和Western blot法均检测到HO-1基因表达随AMN107浓度升高而降低。结论 AMN107可抑制BCR-ABL融合基因和HO-1基因表达,从而诱导慢性粒细胞白血病(CML耐药细胞的凋亡,说明HO-1是CML细胞生长以及BCR-ABL基因存在的一个相关因子,HO-1基因是克服慢性粒细胞白血病耐药的一个潜在靶向。 相似文献
62.
José M. RojasKaty Knight Sarah WatmoughJoanne Bell Lihui WangTherese Callaghan Richard E. Clark 《Leukemia research》2011,35(3):369-372
We and others have reported that vaccination of chronic myeloid leukaemia (CML) patients with e14a2 BCR-ABL junctional peptides can elicit moderate but transient T cell responses. To determine whether CML patients may be tolerised to BCR-ABL, here we used the same schedule to vaccinate 5 healthy subjects. Although IFN-γ and granzyme-B production, and proliferative responses to the vaccine peptides were detected in all 5 cases, responses were statistically similar to CML patients. CML patients are therefore not appreciably tolerised to BCR-ABL, and junctional peptides may only be moderately immunogenic, underlining the importance of antigen immunogenicity when designing vaccination strategies. 相似文献
63.
Chronic myeloid leukemia (CML) is initiated from the BCR-ABL-expressing leukemia stem cells (LSCs). These LSCs are highly resistant to BCR-ABL kinase inhibitors, imatinib, dasantinib and nilotinib, and methods for eradication of LSCs are still not available. It is critical to identify genes that play roles in survival and proliferation of LSCs. We recently discovered that the tumor suppressor gene Pten is downregulated in LSCs of CML mice. By genetic deletion or overexpression of Pten, we confirmed that Pten functions as a tumor suppressor in LSCs of CML, consistent with the role of Pten in LSCs of acute myeloid leukemia (AML) and progenitor cells of T-ALL progenitors. Functional enhancement of the Pten pathway provides a therapeutic strategy for targeting LSCs. 相似文献
64.
《Asian Pacific journal of cancer prevention》2013,14(11):6653-6656
Background: The single most common proto-oncogene change in human neoplasms is a point mutation in RASgenes. A wide range of variation in frequency of KRAS mutations has been seen in hematologic malignancies.Despite this, RAS roles in leukemogenesis remain unclear. The frequency of KRAS mutations in CML has beenreported to be between zero an 10%. Many attempts have been done to develop an anti-RAS drug as a therapeutictarget. . Materials and Methods: This cross sectional study was performed in Mashhad University of MedicalSciences, Mashhad, Iran from 2010-2012. In 78 CML patients (diagnosed according to WHO 2008 criteria)in chronic or accelerated phases, KRAS mutations in codons 12 and 13 were analyzed using a modified PCRrestrictionfragment length polymorphism (RFLP) method. Results: We did not detect any KRAS mutations inthis study. Conclusions: KRAS mutations are overall rare in early phase CML and might be secondary eventshappening late in leukemogenesis cooperating with initial genetic lesions. 相似文献
65.
66.
Marc Delord Philippe Rousselot Jean Michel Cayuela Fran?ois Sigaux Jo?lle Guilhot Claude Preudhomme Fran?ois Guilhot Pascale Loiseau Emmanuel Raffoux Daniela Geromin Emmanuelle Génin Fabien Calvo Heriberto Bruzzoni-Giovanelli 《Oncotarget》2013,4(10):1582-1591
Pharmacogenetic studies in chronic myelogenous leukemia (CML) typically use a candidate gene approach. In an alternative strategy, we analyzed the impact of single nucleotide polymorphisms (SNPs) in drug transporter genes on the molecular response to imatinib, using a DNA chip containing 857 SNPs covering 94 drug transporter genes. Two cohorts of CML patients treated with imatinib were evaluated: an exploratory cohort including 105 patients treated at 400 mg/d and a validation cohort including patients sampled from the 400 mg/d and 600 mg/d arms of the prospective SPIRIT trial (n=239). Twelve SNPs discriminating patients according to cumulative incidence of major molecular response (CI-MMR) were identified within the exploratory cohort. Three of them, all located within the ABCG2 gene, were validated in patients included in the 400 mg/d arm of the SPIRIT trial. We identified an ABCG2 haplotype (define as G-G, rs12505410 and rs2725252) as associated with significantly higher CI-MMR in patients treated at 400 mg/d. Interestingly, we found that patients carrying this ABCG2 “favorable” haplotype in the 400 mg arm reached similar CI-MMR rates that patients randomized in the imatinib 600 mg/d arm. Our results suggest that response to imatinib may be influenced by constitutive haplotypes in drug transporter genes. Lower response rates associated with “non-favorable” ABCG2 haplotypes may be overcome by increasing the imatinib daily dose up to 600 mg/d. 相似文献
67.
68.
Hidehiro Itonaga Hideki Tsushima Daisuke Imanishi Tomoko Hata Yuko Doi Sayaka Mori Daisuke Sasaki Hiroo Hasegawa Emi Matsuo Jun Nakashima Takeharu Kato Makiko Horai Masataka Taguchi Masatoshi Matsuo Hiroaki Taniguchi Junnya Makiyama Shinya Sato Kensuke Horio Koji Ando Yuji Moriwaki Yasushi Sawayama Daisuke Ogawa Reishi Yamasaki Yumi Takasaki Yoshitaka Imaizumi Jun Taguchi Yasuhisa Kawaguchi Shinichiro Yoshida Tatsuro Joh Yukiyoshi Moriuchi Hiroaki Nonaka Hisashi Soda Takuya Fukushima Kazuhiro Nagai Shimeru Kamihira Masao Tomonaga Katsunori Yanagihara Yasushi Miyazaki 《Leukemia research》2014
An appropriate trigger for BCR-ABL1 mutation analysis has not yet been established in unselected cohorts of chronic-phase chronic myelogenous leukemia patients. We examined 92 patients after 12 months of tyrosine kinase inhibitor (TKI) treatment in Nagasaki Prefecture, Japan. Univariate analysis revealed that significant factors associated with not attaining a major molecular response (MMR) were the presence of the minor BCR-ABL1 fusion gene, a low daily dose of TKI, and the emergence of BCR-ABL1 kinase domain mutations conferring resistance to imatinib. Factors associated with the loss of sustained MMR were a low daily dose of TKI and the emergence of alternatively spliced BCR-ABL1 mRNA with a 35-nucleotide insertion. Taken together, our results suggest that the search for BCR-ABL1 mutations should be initiated if patients have not achieved MMR following 12 months of TKI treatment. 相似文献
69.
Fei XH Wu SL Sun RJ Zhou JR Wang JB Wang T Liu HX Wang H Tong CR Wu T Lu DP 《中国实验血液学杂志》2012,20(3):545-548
本研究对2004年1月-2011年2月收治的12例Ph染色体阳性急性髓系白血病(Ph+AML)患者的白血病细胞的形态学、免疫学、细胞遗传学和分子生物学特征及其与生存期的相关性进行分析。Ph+AML的诊断根据WHO标准,且有t(9;22)(q34;q11)或变异的t(9;22)异常,诊断时和诱导治疗后没有CML慢性期的证据。结果表明,12例患者经形态和免疫分型检查确诊8例为AML,4例为髓系及B淋巴细胞系混合细胞白血病。12例患者中除2例初诊时未做染色体检查外其余患者均可检测到Ph染色体,且部分患者伴有复杂染色体或与正常核型共存。在12例患者中均可检测到BCR-ABL阳性,其中b3a2 7例,b2a2 1例,b2a2变异体1例,ela2 2例,e18a2 1例。12例患者经治疗均获得缓解,其中3例患者接受化疗联合格列卫治疗后2例死亡;9例患者进行异基因造血干细胞移植(allo-HSCT),1例患者复发后死亡,1例死于移植后并发症,中位生存期为24(8-80)个月,3年总生存率为(51.4±17.7)%。结论:Ph+AML是一种预后较差的AML,格列卫联合化疗可使患者达完全缓解,缓解后尽快进行HSCT能获得长期生存,改善患者预后。BCR-ABL基因及其变异体的检测为白血病的诊断和治疗提供了更多的机会,可作为初治白血病的常规筛查指标。 相似文献
70.
Tyrosine kinase inhibitors (TKIs) are the mainstay for treatment of chronic myelogenous leukemia (CML). Imatinib was the first
TKI approved for use in CML, but resistance to this therapy has emerged as a significant issue, and second-line options are
often necessary. Increased-dose imatinib may elicit responses in some patients, but clinical evidence suggests only a minority
experience sustained benefit. The second-generation TKIs, dasatinib and nilotinib, have demonstrated efficacy in patients
resistant or intolerant to imatinib. Changes in therapy, with the aim of inducing durable response, should occur promptly
after imatinib failure is identified as all agents are more effective in chronic phase disease than in later stages. Selection
of second-line agents should be driven by efficacy and safety: dasatinib may be more effective in patients with P-loop or
F359C mutations; nilotinib may be more effective in those with F317L mutations. 相似文献