首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   840篇
  免费   36篇
  国内免费   2篇
  878篇
  2024年   5篇
  2023年   8篇
  2022年   10篇
  2021年   28篇
  2020年   15篇
  2019年   16篇
  2018年   27篇
  2017年   19篇
  2016年   27篇
  2015年   59篇
  2014年   49篇
  2013年   59篇
  2012年   70篇
  2011年   73篇
  2010年   57篇
  2009年   29篇
  2008年   44篇
  2007年   52篇
  2006年   42篇
  2005年   40篇
  2004年   31篇
  2003年   34篇
  2002年   19篇
  2001年   7篇
  2000年   3篇
  1999年   2篇
  1998年   8篇
  1997年   2篇
  1996年   4篇
  1995年   6篇
  1994年   3篇
  1993年   3篇
  1992年   1篇
  1991年   4篇
  1989年   1篇
  1988年   1篇
  1985年   4篇
  1984年   2篇
  1982年   2篇
  1981年   3篇
  1980年   2篇
  1979年   2篇
  1978年   1篇
  1977年   1篇
  1976年   1篇
  1975年   2篇
排序方式: 共有878条查询结果,搜索用时 0 毫秒
1.
Until the identification of leptin, the first adipokine discovered in 1994, adipose tissue was considered only as an energy storage tissue. However, it is now clear that adipose tissue is an endocrine/paracrine/autocrine organ, which plays a relevant role in physiopathology of several inflammatory diseases. Actually, it is mainly involved not only in the low-grade inflammatory status in obesity but also in other relevant inflammatory conditions and autoimmune disorders. In this review article, we discuss the main biological activities of leptin, adiponectin, lipocalin-2, resistin, and visfatin, as well as their contributions to certain inflammatory conditions.  相似文献   
2.
This paper describes the patterns and processes of vegetation change and fire history in the Late Holocene (c. 3,140 cal bp) palaeoecological sequence of El Tiemblo, in a mountainous area in central Spain (Gredos range, Spanish Central System), and provides the first Iberian pollen sequence undertaken within a Castanea sativa-dominated woodland. These new data reassess not only the autochthonous nature of the species in the region and in the Iberian Peninsula, but also the naturalness of well-developed sweet chestnut forests. The study focuses on anthropogenic dynamics linked both to the effects of livestock husbandry and the use of fire for forest clearance. With this aim, non-pollen palynomorphs (coprophilous fungi ascospores) and charcoal accumulation rate are useful indicators for assessing the increasing role of human influence on vegetation.  相似文献   
3.
4.
The epidermal growth factor (EGF) is responsible for the activation of intracellular signal transducers that act on cell-cycle progression, cell motility, angiogenesis and inhibition of apoptosis. However, cells can block these effects activating opposite signaling pathways, such as the transforming growth factor beta 1 (TGFβ1) pathway. Thus changes in expression levels of EGF and TGFB1 in renal cells might modulate the renal cell carcinoma (RCC) development, in consequence of changes in regulatory elements of signaling networks such as the microRNAs (miRNAs). Our purpose was to investigate the synergic role of EGF+61G>A and TGFB1+869T>C polymorphisms in RCC development. Genetic polymorphisms were studied by allelic discrimination using real-time PCR in 133 RCC patients vs. 443 healthy individuals. The circulating EGF/EGFR-MAPK-related miR-7, miR-221 and miR-222 expression was analyzed by a quantitative real-time PCR in plasma from 22 RCC patients vs. 27 healthy individuals. The intermediate/high genetic proliferation profile patients carriers present a significantly reduced time-to-progression and a higher risk of an early relapse compared with the low genetic proliferation profile carriers (HR = 8.8, P = 0.038) with impact in a lower overall survival (Log rank test, P = 0.047). The RCC patients presented higher circulating expression levels of miR-7 than healthy individuals (6.1-fold increase, P<0.001). Moreover, the intermediate/high genetic proliferation profile carriers present an increase in expression levels of miR-7, miR-221 and miR-222 during the RCC development and this increase is not observed in low genetic proliferation profile (P<0.001, P = 0.004, P<0.001, respectively). The stimulus to angiogenesis, cell-cycle progression and tumoral cells invasion, through activation of EGFR/MAPK signaling pathway in intermediate/high proliferation profile carriers is associated with an early disease progression, resulting in a poor overall survival. We also demonstrated that the intermediate/high proliferation profile is an unfavorable prognostic factor of RCC and miR-7, miR-221 and miR-222 expressions may be useful phenotype biomarkers of EGFR/MAPK activation.  相似文献   
5.
The vascular cellular adhesion molecule-1 (VCAM-1) is a protein that canonically participates in the adhesion and transmigration of leukocytes to the interstitium during inflammation. VCAM-1 expression, together with soluble VCAM-1 (sVCAM-1) induced by the shedding of VCAM-1 by metalloproteinases, have been proposed as biomarkers in immunological diseases, cancer, autoimmune myocarditis, and as predictors of mortality and morbidity in patients with chronic heart failure (HF), endothelial injury in patients with coronary artery disease, and arrhythmias. This revision aims to discuss the role of sVCAM-1 as a biomarker to predict the occurrence, development, and preservation of cardiovascular disease.  相似文献   
6.
7.
Evolution of ancient satellite DNAs in sturgeon genomes   总被引:1,自引:0,他引:1  
This study characterizes a repetitive DNA family of sequences in sturgeon, the PstI satellite DNA. We have found a high degree of preservation for these sequences, which are present in all 13 species analyzed, including within the genera Acipenser, Huso, and Scaphirhynchus of the family Acipenseridae. This is one of the most ancient satellite DNAs found to date, because it has been estimated to be more than 100 million years old. Alternatively, to the current view that most satellite DNAs are species-specific or preserved in a few closely related species, the PstI family and other previously characterized sturgeon satellite DNA, the HindIII, represent the most fascinating exceptions to the rapid sequence change usually undergone by satellite DNAs. Here, we compare the evolutionary pattern of these two satellite DNA families, PstI and HindIII, which differ markedly in length, sequence, and nucleotide composition. We have found that, in contrast to the situation in most other living beings, a high degree of preservation, a slow sequence change rate and slowed concerted evolution, appears to be a general rule for sturgeon satellite DNAs. The possible causes for all these features are discussed in the light of the evolutionary specifics found within these ancient organisms.  相似文献   
8.
    
The development of heart failure (HF) is characterized by progressive alteration of left ventricle structure and function. Previous works on proteomic analysis in cardiac tissue from patients with HF remain scant. The purpose of our study was to use a proteomic approach to investigate variations in protein expression of left ventricle tissue from patients with ischaemic (ICM) and dilated cardiomyopathy (DCM). Twenty-four explanted human hearts, 12 from patients with ICM and 12 with DCM undergoing cardiac transplantation and six non-diseased donor hearts (CNT) were analysed by 2DE. Proteins of interest were identified by mass spectrometry and validated by Western blotting and immunofluorescence. We encountered 35 differentially regulated spots in the comparison CNT versus ICM, 33 in CNT versus DCM, and 34 in ICM versus DCM. We identified glyceraldehyde 3-phophate dehydrogenase up-regulation in both ICM and DCM, and alpha-crystallin B down-regulation in both ICM and DCM. Heat shock 70 protein 1 was up-regulated only in ICM. Ten of the eleven differentially regulated proteins common to both aetiologies are interconnected as a part of a same network. In summary, we have shown by proteomics analysis that HF is associated with changes in proteins involved in the cellular stress response, respiratory chain and cardiac metabolism. Although we found altered expression of eleven proteins common to both ischaemic and dilated aetiology, we also observed different proteins altered in both groups. Furthermore, we obtained that seven of these eleven proteins are involved in cell death and apoptosis processes, and therefore in HF progression.  相似文献   
9.
10.
    
Kenny-Caffey syndrome (KCS) and the similar but more severe osteocraniostenosis (OCS) are genetic conditions characterized by impaired skeletal development with small and dense bones, short stature, and primary hypoparathyroidism with hypocalcemia. We studied five individuals with KCS and five with OCS and found that all of them had heterozygous mutations in FAM111A. One mutation was identified in four unrelated individuals with KCS, and another one was identified in two unrelated individuals with OCS; all occurred de novo. Thus, OCS and KCS are allelic disorders of different severity. FAM111A codes for a 611 amino acid protein with homology to trypsin-like peptidases. Although FAM111A has been found to bind to the large T-antigen of SV40 and restrict viral replication, its native function is unknown. Molecular modeling of FAM111A shows that residues affected by KCS and OCS mutations do not map close to the active site but are clustered on a segment of the protein and are at, or close to, its outer surface, suggesting that the pathogenesis involves the interaction with as yet unidentified partner proteins rather than impaired catalysis. FAM111A appears to be crucial to a pathway that governs parathyroid hormone production, calcium homeostasis, and skeletal development and growth.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号