全文获取类型
收费全文 | 221篇 |
免费 | 3篇 |
国内免费 | 7篇 |
专业分类
儿科学 | 2篇 |
妇产科学 | 1篇 |
基础医学 | 99篇 |
口腔科学 | 2篇 |
临床医学 | 11篇 |
内科学 | 21篇 |
皮肤病学 | 19篇 |
神经病学 | 4篇 |
特种医学 | 5篇 |
外科学 | 7篇 |
综合类 | 22篇 |
预防医学 | 6篇 |
眼科学 | 4篇 |
药学 | 5篇 |
肿瘤学 | 23篇 |
出版年
2023年 | 10篇 |
2022年 | 6篇 |
2021年 | 12篇 |
2020年 | 18篇 |
2019年 | 14篇 |
2018年 | 12篇 |
2017年 | 4篇 |
2016年 | 1篇 |
2015年 | 6篇 |
2014年 | 18篇 |
2013年 | 14篇 |
2012年 | 11篇 |
2011年 | 16篇 |
2010年 | 11篇 |
2009年 | 4篇 |
2008年 | 6篇 |
2007年 | 5篇 |
2006年 | 4篇 |
2005年 | 4篇 |
2004年 | 5篇 |
2003年 | 2篇 |
2002年 | 1篇 |
2001年 | 2篇 |
2000年 | 6篇 |
1999年 | 3篇 |
1998年 | 5篇 |
1997年 | 8篇 |
1996年 | 1篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 7篇 |
1991年 | 3篇 |
1990年 | 2篇 |
排序方式: 共有231条查询结果,搜索用时 15 毫秒
1.
Dominique Trudel Luminita-Mihaela Avarvarei Michèle Orain Stéphane Turcotte Marie Plante Jean Grégoire Reinhild Kappelhoff David P. Labbé Dimcho Bachvarov Bernard Têtu Christopher M. Overall Isabelle Bairati 《Pathology, research and practice》2019,215(6):152369
Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance. 相似文献
2.
K A Fleming M Evans K C Ryley D Franklin R H Lovell-Badge A L Morey 《The Journal of pathology》1992,167(1):9-17
The sensitivity of non-isotopic in situ hybridization (NISH), particularly on formalin-fixed, paraffin-embedded (FFPE) clinical tissues, has been the subject of controversy. Generally, NISH has been regarded as being less sensitive than radiolabelled procedures, although some reports have contradicted this. Accordingly, tissues from mice which were transgenic for variable amounts of the human alpha-1-antitrypsin gene were used to optimize the NISH procedure and to estimate the sensitivity. This approach showed that prolonged incubation of slides in final substrate resulted in high sensitivity--about 13 kb of target DNA. However, this prolonged incubation crucially depended on achieving minimal non-specific background staining. Many factors affected the degree of background staining, but five were particularly important. First, the method of mounting cut sections onto slides. Second, the length of the probe (ideally less than 400 bp). Third, the procedure for proteolytic digestion. Fourth, the denaturation technique, and fifth, the quality of the dextran sulphate used in the hybridization mix. The optimized protocol showed variable patterns of mRNA distribution in the transgenic mouse livers, while DNA distribution appeared uniform. 相似文献
3.
Jan Schmeller Michael Wessolly Elena Mairinger Sabrina Borchert Thomas Hager Thomas Mairinger Kurt Werner Schmid Jeremias Wohlschlaeger Robert F.H. Walter Fabian D. Mairinger 《Pathology, research and practice》2019,215(2):381-386
Introduction
The usage of formalin-fixed paraffin embedded (FFPE) tissue is characterized by its long shelf-life and simple handling. Therefore it is the most commonly available tissue specimen in routine diagnostics and histological studies. Formaldehyde fixation may result in RNA degradation and cross linking with proteins, while storage conditions also affect RNA integrity. The present study was designed to investigate the influence of these factors on RNA analysis.Design
FFPE-derived RNA from sections of 23 patients with spontaneous pneumothoraxes was used. Unstained sections of FFPE tissue were stored at various temperatures (?80?°C, ?20?°C, 4?°C, 24?°C) prior to RNA extraction. The potential impact on RNA quality of semi-automatic and manual RNA isolation and three different deparaffinization agents (mineral oil, xylene and d-limonene) were compared.Results
The storage temperature of FFPE sections affects RNA concentration and fragmentation, with the optimal storage temperature below -20?°C. The RNA extracted with d-limonene shows equivalent quality to the RNA extracted using more toxic standard agents. The manual isolation provides a higher RNA yield compared to the semi-automatic isolation. However, no differences in the amount of longer RNA fragments were observed. Furthermore, the semi-automatic isolation showed an enhanced RNA quality.Conclusion
FFPE sections not directly used for RNA extraction should be stored below -20?°C to increase quality and yield of the RNA. Usage of semi-automatic isolation produces superior results and simplifies routine processes by having less hands-on-time. Replacement of toxic xylene by d-limonene may contribute to improved occupational safety while not influencing analytical results. 相似文献4.
Domenico Rosace Cristina Gomez-Casado Paloma Fernandez Marina Perez-Gordo María del Carmen Dominguez Angel Vega María Teresa Belver Tania Ramos Francisco Vega Guadalupe Marco Manuel de Pedro Leticia Sanchez María de las Mercedes Arnas Marcela Santaolalla Miguel Ángel Saez Sara Benedé Montserrat Fernandez-Rivas Carlos Blanco Domingo Barber 《The Journal of allergy and clinical immunology》2019,143(2):681-690.e1
5.
Tomomi Yamaguchi Shujiro Hayashi Daisuke Hayashi Takeshi Matsuyama Norimichi Koitabashi Kenichi Ogiwara Masaaki Noda Chiai Nakada Shinya Fujiki Akira Furutachi Yasuhiko Tanabe Michiko Yamanaka Aki Ishikawa Miyako Mizukami Asako Mizuguchi Kazumitsu Sugiura Makoto Sumi Hirokuni Yamazawa Atsushi Izawa Yuko Wada Tomomi Fujikawa Yuri Takiguchi Keiko Wakui Kyoko Takano Shin-Ya Nishio Tomoki Kosho 《American journal of medical genetics. Part A》2023,191(1):37-51
Vascular Ehlers–Danlos syndrome (vEDS) is a hereditary connective tissue disorder (HCTD) characterized by arterial dissection/aneurysm/rupture, sigmoid colon rupture, or uterine rupture. Diagnosis is confirmed by detecting heterozygous variants in COL3A1. This is the largest Asian case series and the first to apply an amplification-based next-generation sequencing through custom panels of causative genes for HCTDs, including a specific method of evaluating copy number variations. Among 429 patients with suspected HCTDs analyzed, 101 were suspected to have vEDS, and 33 of them (32.4%) were found to have COL3A1 variants. Two patients with a clinical diagnosis of Loeys–Dietz syndrome and/or familial thoracic aortic aneurysm and dissection were also found to have COL3A1 variants. Twenty cases (57.1%) had missense variants leading to glycine (Gly) substitutions in the triple helical domain, one (2.9%) had a missense variant leading to non-Gly substitution in this domain, eight (22.9%) had splice site alterations, three (8.6%) had nonsense variants, two (5.7%) had in-frame deletions, and one (2.9%) had a multi-exon deletion, including two deceased patients analyzed with formalin-fixed and paraffin-embedded samples. This is a clinically useful system to detect a wide spectrum of variants from various types of samples. 相似文献
6.
The objective of this study was to evaluate the expression pattern of PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) and its clinical significance in human bladder cancer (BC). 相似文献
7.
Kai Juen Leong Jonathan JamesKaisheng Wen Philippe TaniereDion G. Morton Simon P. BachGlenn M. Matthews 《Experimental and molecular pathology》2013
Background
Formalin fixation, duration of tissue storage and tissue enrichment techniques can affect DNA methylation yield but these effects have not been quantitatively measured. The aim is to investigate the relative impact of these conditions on DNA methylation in rectal cancer.Methods
10 rectal cancers with matched undissected fresh frozen tissues, laser capture microdissected (LCM) formalin-fixed paraffin-embedded (FFPE) tissues, manual macrodissected FFPE tissues, adjacent normal mucosa and stromal tissues were analysed for APC and LINE-1 methylation using bisulphite pyrosequencing.Results
FFPE cancer tissues, which had been stored for at least 4 years showed similar APC and LINE-1 methylation changes to matched fresh frozen cancer tissues. Laser capture microdissection did not increase the degree of methylation detected compared to manual macrodissection. Analysis of stromal tissues showed that they had undergone significant methylation changes compared to adjacent macroscopically normal mucosa, but not to the same extent as cancer tissues.Conclusion
Reliable DNA methylation results can be obtained from FFPE rectal cancer tissues, which have been in long-term storage. Because only minor differences in methylation between macrodissected and LCM cancer tissues were found, our results do not support the routine use of LCM to enrich for cancer cells for DNA methylation studies. 相似文献8.
9.
10.
Jian-Hua Wang Amany Gouda-Vossos Nicolas Dzamko Glenda Halliday Yue Huang 《神经科学通报》2013,29(5):649-654
Both fresh-frozen and formalin-fixed,paraffinembedded(FFPE)human brain tissues are invaluable resources for molecular genetic studies of central nervous system diseases,especially neurodegenerative disorders.To identify the optimal method for DNA extraction from human brain tissue,we compared methods on differently-processed tissues.Fragments of LRRK2 and MAPT(257 bp and 483 bp/245 bp)were amplified for evaluation.We found that for FFPE samples,the success rate of DNA extraction was greater when using a commercial kit than a laboratory-based method(successful DNA extraction from 76%versus 33%of samples).PCR amplicon size and storage period were key factors influencing the success rate of DNA extraction from FFPE samples.In the fresh-frozen samples,the DNA extraction success rate was 100%using either a commercial kit(QIAamp DNA Micro)or a laboratorybased method(sample boiling in 0.1 mol/L NaOH,followed by proteinase K digestion,and then DNA extraction using Chelex-100)regardless of PCR amplicon length or tissue storage time.Although the present results demonstrate that PCR-amplifiable genomic DNA can be extracted from both fresh-frozen and FFPE samples,fresh brain tissue is recommended for DNA extraction in future neuropathological studies. 相似文献