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排序方式: 共有213条查询结果,搜索用时 31 毫秒
1.
Aki Masuzawa Chikako Kiyotani Tomoo Osumi Yoko Shioda Kazutoshi Iijima Osamu Tomita Kazuhiko Nakabayashi Keisuke Oboki Kazuki Yasuda Hiromi Sakamoto Hitoshi Ichikawa Kenichiro Hata Teruhiko Yoshida Kenji Matsumoto Nobutaka Kiyokawa Tetsuya Mori 《European journal of haematology》2014,92(3):263-267
In addition to BCR, various rare fusion partners for the ABL1 gene have been reported in leukemia. We have identified the fusion gene SNX2‐ABL1 in a pediatric case of acute lymphoblastic leukemia (ALL), which has only once previously been reported in an adult patient. Cytogenetic analysis detected this fusion gene arising from a t(5;9)(q22;q34) translocation. ALL cells carrying a SNX2‐ABL1 fusion exhibited a BCR‐ABL1+ ALL‐like gene expression profile. The patient poorly responded to dasatinib but partially responded to imatinib. Treatment using tyrosine kinase inhibitors requires further investigation to optimize the genotype‐based treatment stratification for patients with SNX2‐ABL1 fusion. 相似文献
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Shuichi Ota Toshihiro Matsukawa Satoshi Yamamoto Shinichi Ito Motohiro Shindo Kazuya Sato Takeshi Kondo Kyuhei Kohda Hajime Sakai Akio Mori Tohru Takahashi Hiroshi Ikeda Hiroyuki Kuroda Yoshihito Haseyama Masaki Yamamoto Takeo Sarashina Makoto Yoshida Ryoji Kobayashi Mitsufumi Nishio Toshimichi Ishihara Yasuo Hirayama Yasutaka Kakinoki Hajime Kobayashi Takashi Fukuhara Masahiro Imamura Mitsutoshi Kurosawa 《European journal of haematology》2018,101(1):95-105
4.
Catherine Wilson Katrina Nicholes Daisy Bustos Eva Lin Qinghua Song Jean-Philippe Stephan Donald S. Kirkpatrick Jeff Settleman 《Oncotarget》2014,5(17):7328-7341
Epithelial to mesenchymal transition (EMT) is a key process in embryonic development and has been associated with cancer metastasis and drug resistance. For example, in EGFR mutated non-small cell lung cancers (NSCLC), EMT has been associated with acquired resistance to the EGFR inhibitor erlotinib. Moreover, “EGFR-addicted” cancer cell lines induced to undergo EMT become erlotinib-resistant in vitro. To identify potential therapeutic vulnerabilities specifically within these mesenchymal, erlotinib-resistant cells, we performed a small molecule screen of ~200 established anti-cancer agents using the EGFR mutant NSCLC HCC827 cell line and a corresponding mesenchymal derivative line. The mesenchymal cells were more resistant to most tested agents; however, a small number of agents showed selective growth inhibitory activity against the mesenchymal cells, with the most potent being the Abl/Src inhibitor, dasatinib. Analysis of the tyrosine phospho-proteome revealed several Src/FAK pathway kinases that were differentially phosphorylated in the mesenchymal cells, and RNAi depletion of the core Src/FAK pathway components in these mesenchymal cells caused apoptosis. These findings reveal a novel role for Src/FAK pathway kinases in drug resistance and identify dasatinib as a potential therapeutic for treatment of erlotinib resistance associated with EMT. 相似文献
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Obada T Alhalabi Michael N C Fletcher Thomas Hielscher Tobias Kessler Tolga Lokumcu Ulrich Baumgartner Elena Wittmann Silja Schlue Mona Gttmann Shaman Rahman Ling Hai Lea Hansen-Palmus Laura Puccio Ichiro Nakano Christel Herold-Mende Bryan W Day Wolfgang Wick Felix Sahm Emma Phillips Violaine Goidts 《Neuro-oncology》2022,24(1):39
BackgroundGlioblastoma is the most common primary malignancy of the central nervous system with a dismal prognosis. Genomic signatures classify isocitrate dehydrogenase 1 (IDH)-wildtype glioblastoma into three subtypes: proneural, mesenchymal, and classical. Dasatinib, an inhibitor of proto-oncogene kinase Src (SRC), is one of many therapeutics which, despite promising preclinical results, have failed to improve overall survival in glioblastoma patients in clinical trials. We examined whether glioblastoma subtypes differ in their response to dasatinib and could hence be evaluated for patient enrichment strategies in clinical trials.MethodsWe carried out in silico analyses on glioblastoma gene expression (TCGA) and single-cell RNA-Seq data. In addition, in vitro experiments using glioblastoma stem-like cells (GSCs) derived from primary patient tumors were performed, with complementary gene expression profiling and immunohistochemistry analysis of tumor samples.ResultsPatients with the mesenchymal subtype of glioblastoma showed higher SRC pathway activation based on gene expression profiling. Accordingly, mesenchymal GSCs were more sensitive to SRC inhibition by dasatinib compared to proneural and classical GSCs. Notably, SRC phosphorylation status did not predict response to dasatinib treatment. Furthermore, serpin peptidase inhibitor clade H member 1 (SERPINH1), a collagen-related heat-shock protein associated with cancer progression, was shown to correlate with dasatinib response and with the mesenchymal subtype.ConclusionThis work highlights further molecular-based patient selection strategies in clinical trials and suggests the mesenchymal subtype as well as SERPINH1 to be associated with response to dasatinib. Our findings indicate that stratification based on gene expression subtyping should be considered in future dasatinib trials. 相似文献
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Kiran Naqvi MD Elias Jabbour MD Jeffrey Skinner BS MHA Kristin Anderson BS Sara Dellasala BS Musa Yilmaz MD Alessandra Ferrajoli MD Prithviraj Bose MD Philip Thompson MBBS Yesid Alvarado MD Nitin Jain MBBS Koichi Takahashi MD Jan Burger MD Zeev Estrov MD Gautam Borthakur MBBS Naveen Pemmaraju MD Shilpa Paul Pharm D Jorge Cortes MD Hagop M. Kantarjian MD 《Cancer》2020,126(1):67-75
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The role of Src in prostate cancer. 总被引:3,自引:0,他引:3
K Fizazi 《Annals of oncology》2007,18(11):1765-1773
The Src family kinases (SFKs) are the largest family of nonreceptor protein tyrosine kinases and are responsible for signal transduction during many cellular activities, including differentiation, adhesion, and migration. Aberrant Src/SFK activity has been widely implicated in cancer development. Several lines of evidence indicate a role for SFKs in the development of prostate cancer, e.g. SFK overexpression in prostate cancer cell lines and tissues and reduced cancer cell proliferation, invasion, and migration following Src inhibition. In particular, Src may be involved in androgen-independent growth during advanced stages of disease. Src signaling is also a key pathway during normal and dysregulated bone functioning, and bone metastases are responsible for substantial morbidity in advanced prostate cancer. Src/SFK inhibition therefore represents a potentially useful therapeutic strategy for patients with various stages of prostate cancer. To date, four Src inhibitors have reached clinical trials. Of these, the broadest range of in vitro prostate cancer data are available for dasatinib, which inhibits several SFKs as well as other tyrosine kinases. Src inhibitors may be specifically evaluated in prostate cancer clinical trials in the near future. 相似文献
9.
K. J. Aichberger W. R. Sperr K. V. Gleixner A. Kretschmer P. Valent 《European journal of clinical investigation》2008,38(11):869-873
Background Systemic mastocytosis (SM) is a mast cell neoplasm in which neoplastic cells usually display the D816V‐mutated variant of KIT. Cladribine (2CdA) and dasatinib are two drugs that counteract the in vitro growth of neoplastic mast cells in SM. However, only little is known about the in vivo effects of these drugs in SM. Patient and methods We report on a patient with highly aggressive interferon‐alpha‐resistant SM who was treated with 2CdA and dasatinib. In vitro pretesting revealed a response of neoplastic mast cells to both compounds with reasonable IC50 values. Results The patient was treated with six cycles of 2CdA (0·13 mg kg?1 intravenously daily on 5 consecutive days). Despite a short‐lived major clinical response and a decrease in serum tryptase, the patient progressed to mast cell leukaemia after the sixth cycle of 2CdA. The patient then received two further courses of 2CdA followed by treatment with dasatinib (100 mg per os daily). However, no major response was obtained and the patient died from disease progression after 2 months. Conclusions In a patient with rapidly progressing aggressive SM, neither 2CdA nor dasatinib produced a long‐lasting response in vivo, despite encouraging in vitro results. For such patients, alternative treatment strategies have to be developed. 相似文献
10.
Aichberger KJ Herndlhofer S Agis H Sperr WR Esterbauer H Rabitsch W Knöbl P Haas OA Thalhammer R Schwarzinger I Sillaber C Jäger U Valent P 《European journal of clinical investigation》2007,37(10):808-813
BACKGROUND: Central nervous system (CNS) relapse in chronic myeloid leukaemia (CML) is rare and if recorded is usually found to occur in patients with lymphoblastic transformation. The BCR/ABL tyrosine kinase inhibitor imatinib is highly effective in patients with CML, but hardly crosses the blood-brain barrier. PATIENTS AND METHODS: We report on two CML patients who developed a myeloid CNS relapse during treatment with imatinib. One patient was in major cytogenetic response at the time of CNS relapse. In both cases, the myeloid origin of neoplastic cells in the cerebrospinal fluid (CSF) was demonstrable by immunophenotyping, and their leukaemic origin by detection of the BCR/ABL oncoprotein. No BCR/ABL kinase domain mutations were found. Both patients received intrathecal liposomal cytarabine (50 mg each cycle; 6 cycles). In one patient, additional CNS radiation was performed, whereas in the other, consecutive treatment with dasatinib (70 mg per os twice daily) was started. RESULTS: In response to therapy, the clinical symptoms resolved, and the leukaemic cells in the CSF disappeared in both cases. After three months of observation, both patients are in complete cytogenetic and major molecular response, without evidence for a systemic or a CNS relapse. CONCLUSIONS: 'Anatomic' resistance against imatinib in the CNS can lead to a myeloid CNS relapse. Liposomal cytarabine with or without radiation is effective as local therapy in these patients. For systemic treatment and prophylaxis, BCR/ABL kinase inhibitors crossing the blood-brain barrier such as dasatinib should be considered in patients with CNS relapse. 相似文献