全文获取类型
收费全文 | 1342篇 |
免费 | 142篇 |
国内免费 | 18篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 22篇 |
妇产科学 | 23篇 |
基础医学 | 234篇 |
口腔科学 | 22篇 |
临床医学 | 68篇 |
内科学 | 187篇 |
皮肤病学 | 26篇 |
神经病学 | 42篇 |
特种医学 | 13篇 |
外科学 | 57篇 |
综合类 | 96篇 |
预防医学 | 60篇 |
眼科学 | 8篇 |
药学 | 172篇 |
中国医学 | 53篇 |
肿瘤学 | 416篇 |
出版年
2024年 | 9篇 |
2023年 | 37篇 |
2022年 | 55篇 |
2021年 | 60篇 |
2020年 | 74篇 |
2019年 | 79篇 |
2018年 | 51篇 |
2017年 | 62篇 |
2016年 | 47篇 |
2015年 | 61篇 |
2014年 | 108篇 |
2013年 | 84篇 |
2012年 | 85篇 |
2011年 | 109篇 |
2010年 | 86篇 |
2009年 | 62篇 |
2008年 | 60篇 |
2007年 | 65篇 |
2006年 | 57篇 |
2005年 | 48篇 |
2004年 | 31篇 |
2003年 | 30篇 |
2002年 | 34篇 |
2001年 | 21篇 |
2000年 | 12篇 |
1999年 | 6篇 |
1998年 | 10篇 |
1997年 | 13篇 |
1996年 | 5篇 |
1995年 | 6篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有1502条查询结果,搜索用时 15 毫秒
1.
《Best Practice & Research: Clinical Haematology》2019,32(1):3-12
Therapy-related myeloid neoplasm (t-MN) is a rare but devastating consequence of chemotherapy and/or radiotherapy used for the treatment of solid cancers and various hematologic malignancies. Our current understanding of the etiology is that hematopoietic clones that are contemporaneous with the primary cancer and resistant to the cytotoxic exposure have the potential to undergo selective expansion and transformation to t-MN. Consequently, a large proportion of cases are associated with adverse risk factors, resulting in limited effective treatment options. Despite the emergence of some therapies with promising activity in t-MN, most effects are short-lived and allogeneic stem cell transplantation remains the only curative option for eligible patients. This review summarizes the current literature on t-AML and t-MDS, with the aim of providing practical recommendations on the clinical evaluation and management of these conditions. 相似文献
2.
M. Eiro T. Katoh F. Ushikubi S. Narumiya T. Watanabe 《Clinical and experimental nephrology》2002,6(2):85-90
Background. Thromboxane (TX) A2 inhibition or prostaglardin (PGI2) infusion prevents ischemic acute renal failure (ARF) in animal models. However, the pathophysiological roles of the prostanoid
receptors in the development of ischemic ARF are not fully understood, partly because of the limited specificity of their
inhibitors or antagonists.
Methods. We investigated whether targeted disruption of the PGI2 receptor (IP) or TXA2 receptor (TP) genes conferred susceptibility to renal ischemic-reperfusion injury, using IP and TP knockout mice.
Results. Serum creatinine concentration in TP knockout mice was not significantly different from that in wild-type controls. There
were no significant histological differences between TP knockout and wild-type mice. Likewise, IP knockout mice showed no
significant differences from the wild-type controls in regard to creatinine concentration or histological damage.
Conclusions. Lack of TP or IP had no influence on postischemic ARF in mice, indicating that receptors for TXA2 or PGI2 may have minimal roles in the development of this mouse model of ischemic ARF.
Received: July 5, 2001 / Accepted: April 8, 2002 相似文献
3.
Aasmund Berner Gry Geitvik Frank Karlsen Sophie D. Foss Jahn M. Nesland Anne-Lise B
Rresen 《The Journal of pathology》1995,176(3):299-308
The TP53 gene mutation pattern in prostatic cancer was examined in relation to progression and survival, using archival formalin-fixed pre-and post-treatment tumour specimens from 84 prostatic cancer patients. Thirty-four had hormone-sensitive tumours and 50 were hormone-resistant. Six of the 34 (18 per cent) therapy-responding tumours and 19 of the 50 (38 per cent) hormone-resistant tumours showed p53 protein accumulation in the post-treatment specimen. Both pre- and post-treatment specimens from these 25 patients were analysed for mutation of the conserved regions of the TP53 gene (exons 5–8), using constant denaturant gel electrophoresis (CDGE) followed by DNA sequencing. In the post-treatment samples, mutations were detected in three of the six patients with hormone-responsive tumours and in 11 of the 19 patients with hormone-resistant tumours. The three (100 per cent) patients with therapy-responsive tumours with mutations and nine of the 11 (82 per cent) patients with therapy-resistant tumours with mutations died of the disease. Thirteen of the 14 mutations in the post-treatment specimens were transitions, 11 occurring at CpG dinucleotides in which codon 273 was involved in ten. A significantly higher proportion of tumours with mutations were poorly differentiated compared with tumours without mutation (P<0·04). Our findings indicate that TP53 mutation is a late event in tumour development of the prostate gland and that codon 273 might be a ‘hotspot’ for mutation in the progression of the disease. 相似文献
4.
<正>随着高通量测序技术的发展,成千上万种长链非编码RNA(long non-coding RNA,lncRNA)进入人们的视野。lncRNA是一类长度超过200个核苷酸并缺少开放阅读框的不具备蛋白质编码功能的RNA~([1-2])。研究发现lncRNA参与诸多生物学进程的关键步骤,包括染色质重塑、基因转录、转录后调节和蛋白质翻译等~([3-5])。LncRNA机制的不断被阐明,也为肿瘤的研究提供了新的可能。LncRNA在多种肿瘤的增殖、迁移侵袭和抗凋亡 相似文献
5.
6.
Chromosome aberrations in B-cell chronic lymphocytic leukemia: reassessment based on molecular cytogenetic analysis 总被引:13,自引:0,他引:13
Döhner H Stilgenbauer S Döhner K Bentz M Lichter P 《Journal of molecular medicine (Berlin, Germany)》1999,77(2):266-281
In B-cell chronic lymphocytic leukemia (B-CLL) clonal chromosome aberrations are detected in approximately 40–50% of tumors
when using conventional chromosome banding analysis. Most studies find trisomy 12 to be the most frequent chromosome aberration,
followed by structural aberrations of the long arm of chromosomes 13 and 14. Trisomy 12 and the ”14q+” marker are associated
with shorter survival times, while the patients with 13q abnormalities have a favorable outcome, similar to those with a normal
karyotype. The development of molecular cytogenetic techniques has greatly improved our ability to detect chromosome aberrations
in tumor cells. Using fluorescence in situ hybridization, chromosome aberrations can be detected not only in dividing cells
but also in interphase nuclei, an approach referred to as interphase cytogenetics. The prevalence of specific aberrations in B-CLL is currently being reassessed by interphase cytogenetics. By far the most
frequent abnormality are deletions involving chromosome band 13q14, followed by deletions of the genomic region 11q22.3-q23.1,
trisomy 12, deletions of 6q21-q23, and deletions/mutations of the TP53 tumor suppressor gene at 17p13. The evaluation of the true incidence of these aberrations now provides the basis for more
accurate correlations with clinical characteristics and outcome. Deletions/mutations of the TP53 gene have been shown to be associated with resistance to treatment and to be an independent marker for poor survival. 11q
deletions have been associated with extensive nodal involvement, rapid disease progression, and short survival times. Whether
trisomy 12, 13q14, and 6q deletions have a prognostic impact awaits further study. The application of these molecular cytogenetic
techniques will also contribute to the identification of the pathogenetically relevant genes that are affected by the chromosome
aberrations in B-CLL.
Received: 2 February 1998 / Accepted: 31 March 1998 相似文献
7.
8.
Michael Krawczak Birgitte Smith-Sorensen Jrg Schmidtke Vijay V. Kakkar David N. Cooper Eivind Hovig 《Human mutation》1995,5(1):48-57
The spectrum of somatic TP53 single basepair substitutions detected in 955 cancers was compared with that of 2,224 different germline mutations in 279 different human genes (other than TP53), reported as the cause of inherited disease. This comparison reveals that, disregarding a relatively small subset (12%) of TP53 mutations that probably result from the action of exogenous mutagens, both the relative rates and the nearest-neighbor spectra of single basepair substitutions are similar in the two datasets. This spectral resemblance suggests that a substantial proportion of cancer-associated somatic TP53 mutations result from endogenous cellular mechanisms. The likelihood of clinical observation of a particular mutation type differs, however, between tumors and genetic diseases, when the chemical properties of the resulting amino acid substitutions are considered. Together with a sixfold higher observation likelihood for mutations at evolutionary conserved residues, this finding argues that selection is a critical factor in determining which TP53 mutations are found to be associated with human cancer. © 1995 Wiley-Liss, Inc. 相似文献
9.
目的分析人类免疫缺陷病毒(HIV)感染者中合并乙型肝炎病毒(HBV)、丙型肝炎病毒(HCV)以及梅毒螺旋体(TP)感染的流行现状及其特点。方法对确诊的184例HIV感染者进行流行病学调查,并采集血标本进行HBV、HCV和梅毒血清学检测。结果HIV感染者感染途径分别为:静脉注射毒品44.0%,性传播20.1%,母婴传播4.3%,输血或血制品3.8%,其他(原因不详)27.7%。184例HIV感染者中,抗-HCV阳性者36人(19.6%),HBsAg阳性者29人(15.8%),梅毒感染者21人(11.4%)。HIV、HBV和HCV三重感染者9人,约占4.9%。结论柳州市HIV感染以静脉注射毒品为主,性传播有所上升,HIV感染正由特殊人群向普通人群蔓延。HIV合并HBV、HCV、TP感染较为常见。建议在性病门诊中常规开展HIV的筛查,对HIV感染者常规进行HBV、HCV的相关检查并积极采取相关的预防治疗措施。 相似文献
10.
Karen B Jourdan Timothy W Evans Nicholas P Curzen Jane A Mitchell 《British journal of pharmacology》1997,120(7):1280-1285
- 8-Iso prostaglandin F2α (8-iso PGF2α) is one of a series of prostanoids formed independently of the cyclo-oxygenase pathway. It has been shown to be upregulated in many conditions of oxidant stress where its formation is induced by free radical-catalysed actions on arachidonic acid. As 8-iso PGF2α is formed in vivo in diseases in which oxidant stress is high such as septic shock, we have assessed the relative potency and efficacy of this compound in pulmonary arteries from control and lipopolysaccharide (LPS)-treated rats.
- Several studies have characterized the contractile actions of 8-iso PGF2α on various smooth muscle preparations, but its potential dilator actions have not been addressed. Thus these studies examined both the contractile and dilator actions of 8-iso PGF2α in rat pulmonary artery rings. The thromboxane mimetic U46619, PGE2 sodium nitroprusside (SNP) and acetyl choline (ACh) were used for comparison. Each prostanoid had to be dissolved in ethanol to a maximum concentration of 1×10−2 M. At high concentrations, ethanol directly contracted pulmonary vessels. We were therefore limited by the actions of the vehicle such that we were unable to add prostanoids at concentrations higher than 1×10−4 M. In some cases this meant that maximum responses were not achieved and in these cases the Emax and pD2 values are apparent estimates.
- The following rank order of potency was obtained from contractile studies; U46619>8-iso PGF2α>PGE2, each prostanoid producing concentration-dependent contractions (10−103×10−4 M, 10−910−4 M, 10−810−4 M, respectively). As has been shown previously for other smooth muscle preparations, the thromboxane receptor (TP) antagonist ICI 192605, (1×10−6, 1×10−5 and 1×10−4 M), inhibited the contractions of 8-iso PGF2α in a concentration-dependent fashion.
- The nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 1×10−4 M), enhanced the contractile function of both 8-iso PGF2α and PGE2, but had no effect on that caused by U46619. Similarly, L-NAME inhibited the dilator function of all agents tested except the exogenous nitric oxide (NO) donor SNP, indicating that PGE2 and 8-iso PGF2α like ACh, act through the release of NO. The specificity of the effects of L-NAME were confirmed in studies with the inactive enantiomer D-NAME (1×10−4 M), which did not affect the contractile or the dilator actions of 8-iso PGF2α. Furthermore, ICI 192605 enhanced the dilator actions of 8-iso PGF2α, suggesting that the dilator component of 8-iso PGF2α was achieved via activation of a non-TP receptor.
- Isoprostanes may modulate vascular tone by a direct action on TP receptors to cause contraction and via a distinct receptor leading to the release of NO to cause dilatation.