全文获取类型
收费全文 | 427篇 |
免费 | 68篇 |
国内免费 | 16篇 |
专业分类
儿科学 | 2篇 |
妇产科学 | 10篇 |
基础医学 | 36篇 |
口腔科学 | 7篇 |
临床医学 | 16篇 |
内科学 | 40篇 |
皮肤病学 | 4篇 |
神经病学 | 2篇 |
特种医学 | 1篇 |
外科学 | 22篇 |
综合类 | 32篇 |
预防医学 | 1篇 |
眼科学 | 1篇 |
药学 | 35篇 |
中国医学 | 3篇 |
肿瘤学 | 299篇 |
出版年
2024年 | 2篇 |
2023年 | 11篇 |
2022年 | 3篇 |
2021年 | 32篇 |
2020年 | 25篇 |
2019年 | 35篇 |
2018年 | 22篇 |
2017年 | 23篇 |
2016年 | 23篇 |
2015年 | 69篇 |
2014年 | 59篇 |
2013年 | 40篇 |
2012年 | 28篇 |
2011年 | 23篇 |
2010年 | 24篇 |
2009年 | 16篇 |
2008年 | 9篇 |
2007年 | 14篇 |
2006年 | 10篇 |
2005年 | 13篇 |
2004年 | 6篇 |
2003年 | 5篇 |
2002年 | 6篇 |
2001年 | 2篇 |
2000年 | 3篇 |
1999年 | 4篇 |
1998年 | 3篇 |
1995年 | 1篇 |
排序方式: 共有511条查询结果,搜索用时 31 毫秒
1.
Tianyu Zeng Yijia Hua Chunxiao Sun Yuchen Zhang Fan Yang Mengzhu Yang Yiqi Yang Jun Li Xiang Huang Hao Wu Ziyi Fu Wei Li Yongmei Yin 《International journal of cancer. Journal international du cancer》2020,147(11):3007-3018
tRNA-derived fragments, a class of small noncoding RNAs (sncRNAs), have been identified in numerous studies in recent years. tRNA-derived fragments are classified into two main groups, including tRNA halves (tiRNAs) and tRNA-derived small RNA fragments (tRFs), according to different cleavage positions of the precursor or mature tRNAs. Instead of random tRNA degradation debris, a growing body of evidence has shown that tRNA-derived fragments are precise products of specific tRNA modifications and play important roles in biological activities, such as regulating protein translation, affecting gene expression, and altering immune signaling. Recently, the relations between tRNA-derived fragments and the occurrence of human diseases, especially cancers, have generated wide interest. It has been demonstrated that tRNA-derived fragments are involved in cancer cell proliferation, metastasis, progression and survival. In this review, we will describe the biogenesis of tRNA-derived fragments, the distinct expression and function of tRNA-derived fragments in the development of cancers, and their emerging roles as diagnostic and prognostic biomarkers and precise targets of future treatments. 相似文献
2.
The overwhelming problem of cutaneous melanoma is chemoresistance. Subversion of the biochemical changes that lead to chemoresistance
intersects the apoptosis pathways. The mitochondrion has been a focal point of this intersection for the development of therapeutic
strategies aimed at reducing the progression of melanoma. The Bcl-2 family of apoptotic regulators is arguably the most pivotal
component to this mitochondrial response. The shear number of studies conducted on the relationship between melanoma and Bcl-2
members prompted us to evaluate the literature available and discern some rational utility of the data. We have found that
there are striking inconsistencies for the expression of Bcl-2 family proteins with melanoma progression, particularly for
Bcl-2. Roughly one-third of the data suggests an increase in Bcl-2 expression with advancing melanoma, while another third
suggests a decrease. Furthermore, the remaining third found on the whole, a detectable level of Bcl-2 in all tissues of melanocytic
origin. These discrepancies are difficult to rectify in light of the apparent success of recent clinical trials utilizing
Bcl-2 antisense strategies. The general consensus in the literature is that pro-apoptotic Bax is decreased with melanoma progression
while anti-apoptotic Bcl-xL and Mcl-1 appear to increase with progression. We suggest that the biochemical techniques being used for analysis present
too great of a heterogeneity, which could be mitigated with more standard procedures and reagents. Finally the utility of
‘multi-specific’ antisense tactics could be a more effective way of targeting advanced melanoma disease.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
3.
在建立了耐顺铂 (CDDP) 的卵巢癌细胞的基础上, 探讨了敏感及耐药的卵巢癌细胞株胞膜上的ATP酶(ATPase) 活性。结果表明: 两株肿瘤细胞膜上的Na+ 、K+ -ATPase 和Ca2+ 、Mg2+ -ATPase 活性均被抑制后, 耐药细胞膜上的ATPase活性明显高于敏感细胞(P< 0.05), 而且该ATPase活性可在维拉帕米(VPM) 作用下进一步增高,与未加VPM 的耐药细胞相比差异有显著性(P< 0.05)。提示肿瘤细胞耐药的产生可能与细胞膜上的ATPase活性改变有关。 相似文献
4.
Makoto Okada Junzo Kigawa Yukihisa Minagawa Yasunobu Kanamori Hiroaki Itamochi Xiusi Cheng Tetsuro Ohishi Naoki Terakawa 《International journal of clinical oncology / Japan Society of Clinical Oncology》1998,3(4):240-246
Background A role for theTP53 (alias p53) tumor-suppressor gene in chemoresistance has recently been discussed, but little is known about the clinical
relevance of theTP53 gene to chemoresistance. To elucidate the relevance ofTP53 status to chemoresistance, we investigated theTP53 gene and TP53 protein expression in tumors from the same patients, before and after chemotherapy.
Methods Twenty-one patients with ovarian cancer, who had residual disease after primary surgery, were studied. These patients received
chemotherapy consisting of cisplatin, doxorubicin, and cyclophosphamide, and then underwent a second surgery. Polymerase chain
reaction-single strand conformation polymorphism analysis and cycle sequencing were performed to determineTP53 mutation. TP53 protein was detected by Western blot analysis.
Results Of the 21 patients studied, 9 responded to chemotherapy. Mutation of theTP53 gene was seen in 7 patients (2 responders and 5 nonresponders) before chemotherapy. After chemotherapy, another mutation
of the gene was observed in 5 patients, all of whom were nonresponders. TP53 protein was detected in 10 patients (3 responders
and 7 nonresponders) before chemotherapy. After chemotherapy, the expression of TP53 protein increased in these 3 nonresponders,
and became positive in 2 other nonresponders.
Conclusions This study showed for the first time in clinical investigation that alterations toTP53 could develop in association with chemotherapy, and thatTP53 status may relate to the mechanisms of chemoresistance in patients with epithelial ovarian cancer. 相似文献
5.
Reduced apoptosis and proliferation and increased Bcl-2 in residual breast cancer following preoperative chemotherapy 总被引:10,自引:0,他引:10
P.A. Ellis I.E. Smith S. Detre S.A. Burton J. Salter R. A'Hern G. Walsh S.R.D. Johnston M. Dowsett 《Breast cancer research and treatment》1998,48(2):107-116
Experimental laboratory data suggest that tumour growth is a balance between apoptosis and proliferation and that suppression of drug-induced apoptosis by oncogenes such as bcl-2 may be an important cause of intrinsic chemoresistance. The aims of this study were to assess the in vivo relationship of apoptosis to proliferation and Bcl-2 protein in human breast tumours both prior to chemotherapy and in the residual resistant cell population at the completion of treatment. We examined apoptotic index (AI), Ki67 and Bcl-2 protein expression in the tissue of 40 patients with operable breast cancer immediately before ECF preoperative chemotherapy, and in 20 of these patients with residual tumour, at the completion of treatment. There was a significant positive association between AI and Ki67 both before and after chemotherapy, and in their percentage change with treatment. In the residual specimens AI and Ki67 were significantly reduced compared with pre-treatment biopsies, while Bcl-2 expression showed a significant increase. No differences were seen in the pre-treatment levels of any of the variables measured between patients obtaining pathological complete response and those who did not, although numbers were small. These data suggest that apoptosis and proliferation are closely related in vivo. It is possible that the phenotype of reduced apoptosis and proliferation, and increased Bcl-2 may be associated with breast cancer cells resistant to cytotoxic chemotherapy, although this can only be proven by assessing larger numbers of patients in relation to pathological response. 相似文献
6.
PURPOSE: We describe the establishment and preliminary characterization of a cell line designated SCRC-1, which was derived from a primary renal small cell carcinoma. MATERIALS AND METHODS: Continuous cultures of a primary stage IVa renal small cell carcinoma and a xenograft in nude mice derived therefrom were characterized by immunohistology, electron microscopy, immunofluorescence/flow cytometry, cytogenetic analysis, and an in vitro drug resistance assay. RESULTS: SCRC-1 cells were reactive with antibodies to NSE, chromogranin-A, bombesin, Bcl-2, CD44s, CD44v6, CD44v7 to 8, vimentin and S100 protein (predominantly beta-subunit), and were unreactive with antibodies to EMA, CD54, EGFR(R1), URO-5, URO-7, URO-8 and URO-10. A similar immunoprofile was also found in both the primary tumor and the xenograft. Cytogenetic analysis revealed the following common clonal aberrations in all 50 metaphases analyzed: 45, XX, t (X;10;18) (p11;p11;q11), -der(18)t(X;10;18), indicating the clonal nature of this neoplasm. SCRC-1 cells showed low drug resistance to cyclophosphamide, doxorubicin, gemcitabine and fluorouracil, intermediate resistance to carmustine and mitomycin-C, and extreme resistance to cisplatin. CONCLUSION: We have documented the initial characterization of SCRC-1, which may be the first cell line reported to be derived from a primary small cell carcinoma of the kidney. This cell line can be used for further studies uncovering the biology and histogenesis of this rare cancer and delineating differences among small cell carcinomas of the kidney and other histological types. 相似文献
7.
8.
9.
《Expert review of anticancer therapy》2013,13(8):893-899
Epithelial ovarian carcinoma consists of several subtypes, including high-grade and low-grade serous carcinoma. In the recent past, women with all subtypes of epithelial ovarian carcinoma have been treated similarly and are included in the same clinical trials. However, a distinction has emerged between the type I, low-grade tumors and the type 2, higher-grade epithelial malignancies. Low-grade serous carcinoma exhibits different molecular and clinical features from the other epithelial subtypes, as well as some degree of chemotherapy resistance. This review summarizes the genetic, molecular and clinical characteristics of low-grade serous disease and provides an appraisal of the management strategies 相似文献
10.
Let‐7c restores radiosensitivity and chemosensitivity and impairs stemness in oral cancer cells through inhibiting interleukin‐8 下载免费PDF全文