全文获取类型
收费全文 | 941篇 |
免费 | 63篇 |
国内免费 | 54篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 34篇 |
妇产科学 | 34篇 |
基础医学 | 202篇 |
口腔科学 | 10篇 |
临床医学 | 29篇 |
内科学 | 186篇 |
皮肤病学 | 9篇 |
神经病学 | 134篇 |
特种医学 | 7篇 |
外科学 | 70篇 |
综合类 | 46篇 |
预防医学 | 43篇 |
眼科学 | 12篇 |
药学 | 85篇 |
中国医学 | 5篇 |
肿瘤学 | 147篇 |
出版年
2023年 | 20篇 |
2022年 | 56篇 |
2021年 | 74篇 |
2020年 | 51篇 |
2019年 | 47篇 |
2018年 | 76篇 |
2017年 | 57篇 |
2016年 | 63篇 |
2015年 | 74篇 |
2014年 | 102篇 |
2013年 | 90篇 |
2012年 | 58篇 |
2011年 | 98篇 |
2010年 | 44篇 |
2009年 | 42篇 |
2008年 | 31篇 |
2007年 | 25篇 |
2006年 | 31篇 |
2005年 | 5篇 |
2004年 | 10篇 |
2003年 | 3篇 |
2000年 | 1篇 |
排序方式: 共有1058条查询结果,搜索用时 31 毫秒
61.
Rebecca C. Richmond Aleef Al-Amin George Davey Smith Caroline L. Relton 《Early human development》2014
Large-scale population-based birth cohorts, which recruit women during pregnancy or at birth and follow up their offspring through infancy and into childhood and adolescence, provide the opportunity to monitor and model early life exposures in relation to developmental characteristics and later life outcomes. However, due to confounding and other limitations, identification of causal risk factors has proved challenging and published findings are often not reproducible. A suite of methods has been developed in recent years to minimise problems afflicting observational epidemiology, to strengthen causal inference and to provide greater insights into modifiable intra-uterine and early life risk factors. The aim of this review is to describe these causal inference methods and to suggest how they may be applied in the context of birth cohorts and extended along with the development of birth cohort consortia and expansion of “omic” technologies. 相似文献
62.
63.
64.
The acquisition of reproductive competence is organized and activated by steroid hormones acting upon the hypothalamus during critical windows of development. This review describes the potential role of epigenetic processes, particularly DNA methylation, in the regulation of sexual differentiation of the hypothalamus by hormones. We examine disruption of these processes by endocrine-disrupting chemicals (EDCs) in an age-, sex-, and region-specific manner, focusing on how perinatal EDCs act through epigenetic mechanisms to reprogram DNA methylation and sex steroid hormone receptor expression throughout life. These receptors are necessary for brain sexual differentiation and their altered expression may underlie disrupted reproductive physiology and behavior. Finally, we review the literature on histone modifications and non-coding RNA involvement in brain sexual differentiation and their perturbation by EDCs. By putting these data into a sex and developmental context we conclude that perinatal EDC exposure alters the developmental trajectory of reproductive neuroendocrine systems in a sex-specific manner. 相似文献
65.
Epigenetics and Epigenetic Alterations in Pancreatic Cancer 总被引:1,自引:0,他引:1
Noriyuki Omura Michael Goggins 《International journal of clinical and experimental pathology》2009,2(4):310-326
Pancreatic cancer remains a major therapeutic challenge. In 2008, there will be approximately 37,680 new cases and 34,290 deaths attributable to pancreatic cancer in the United States (U.S.), making it the fourth leading cause of cancer-related death. Recent comprehensive pancreatic cancer genome project found that pancreatic adenocarcinomas harbored 63 intragenic mutations or amplifications/homozygous deletions and these alterations clustered in 12 signaling pathways. In addition to widespread genetic alterations, it is now apparent that epigenetic mechanisms are also central to the evolution and progression of human cancers. Since epigenetic silencing processes are mitotically heritable, they can drive neoplastic progression and undergo the same selective pressure as genetic alterations. This review will describe recent developments in cancer epigenetics and their importance in our understanding of pancreatic adenocarcinomas. 相似文献
66.
A balance between rapid, short lived, neuronal responses and prolonged ones fulfill the biochemical and cellular requirements for creating a molecular memory. I provide an overview of epigenetic mechanisms in the brain and discuss their impact on synaptic plasticity, cognitive functions, and discuss a recent example of how they can contribute to neurodegeneration and the cognitive decline associated with Alzheimer's disease. 相似文献
67.
68.
69.
70.
Molecular studies of many types of cancer have revealed that clinically evident tumours carry multiple genetic and epigenetic abnormalities, including DNA sequence alterations, chromosome copy number changes and aberrant promoter hypermethylation. Together, these aberrant changes result in the activation of oncogenes and inactivation of tumour-suppressor genes (TSG). In many cases these abnormalities can be found in premalignant lesions and even in histological normal adjacent cells. Many tumour types are difficult to detect early and are frequently resistant to available chemotherapy and radiotherapy. Therefore, the early detection, chemoprevention and the design of new therapeutic strategies based on the increased understanding of cancer molecular changes are one of the great challenges nowadays. Insertions of a methyl group at the fifth carbon of cytosines within the dinucleotide 5'- CpG-3' is the best studied epigenetic mechanism. DNA methylation acts together with others mechanisms like histone modification, chromatin remodelling and microRNAs to mould the DNA structure according to the functional state required. The aberrant methylation of the CpG islands located at the promoter region of specific genes is a common and early event involved in cancer development. Thus, hypermethylated DNA sequences from tumours are one of the most promising markers for early detection screenings as well as tumour classification and chemotherapy response in many types of cancer. 相似文献