全文获取类型
收费全文 | 1611篇 |
免费 | 51篇 |
出版年
2023年 | 27篇 |
2022年 | 22篇 |
2021年 | 46篇 |
2020年 | 33篇 |
2019年 | 49篇 |
2018年 | 45篇 |
2017年 | 49篇 |
2016年 | 55篇 |
2015年 | 58篇 |
2014年 | 107篇 |
2013年 | 120篇 |
2012年 | 125篇 |
2011年 | 157篇 |
2010年 | 99篇 |
2009年 | 74篇 |
2008年 | 89篇 |
2007年 | 93篇 |
2006年 | 87篇 |
2005年 | 81篇 |
2004年 | 73篇 |
2003年 | 58篇 |
2002年 | 52篇 |
2001年 | 11篇 |
2000年 | 10篇 |
1999年 | 3篇 |
1998年 | 6篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 1篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1987年 | 1篇 |
1986年 | 3篇 |
1982年 | 2篇 |
1979年 | 1篇 |
1964年 | 1篇 |
1963年 | 1篇 |
1891年 | 2篇 |
1889年 | 1篇 |
排序方式: 共有1662条查询结果,搜索用时 46 毫秒
1.
Sohel Md Mahmodul Hasan Akyuz Bilal Konca Yusuf Arslan Korhan Gurbulak Kutlay Abay Murat Kaliber Mahmut Cinar Mehmet Ulas 《Mammalian genome》2020,31(9-12):309-324
Mammalian Genome - Maternal nutrition during pregnancy is one of the major intrauterine environmental factors that influence fetal development by significantly altering the expression of genes that... 相似文献
2.
Chromosoma - Cyclins, as regulatory partners of cyclin-dependent kinases (CDKs), control the switch-like cell cycle transitions that orchestrate orderly duplication and segregation of genomes.... 相似文献
3.
Kazim Sahin Mehmet Tuzcu Cemal Orhan Hasan Gencoglu Mustafa Ulas Mustafa Atalay Nurhan Sahin Armagan Hayirli James R. Komorowski 《Biological trace element research》2012,150(1-3):291-296
The objective of this experiment was to investigate the effects of supplemental chromium picolinate (CrPic) and chromium histidinate (CrHis) on nuclear factor-kappa B (NF-??B p65) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway in diabetic rat brain. Nondiabetic (n?=?45) and diabetic (n?=?45) male Wistar rats were either not supplemented or supplemented with CrPic or CrHis via drinking water to consume 8???g elemental chromium (Cr) per day for 12?weeks. Diabetes was induced by streptozotocin injection (40?mg/kg i.p., for 2?weeks) and maintained by high-fat feeding (40?%). Diabetes was associated with increases in cerebral NF-??B and 4-hydroxynonenal (4-HNE) protein adducts and decreased in cerebral nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha (I??B??) and Nrf2 levels. Both Cr chelates were effective to decrease levels of NF-??B and 4-HNE protein adducts and to increase levels of I??B?? and Nrf2 in the brain of diabetic rats. However, responses of these increases and decreases were more notable when Cr was supplemented as CrHis than as CrPic. In conclusion, Cr may play a protective role in cerebral antioxidant defense system in diabetic subjects via the Nrf2 pathway by reducing inflammation through NF-??B p65 inhibition. Histidinate form of Cr was superior to picolinate form of Cr in reducing NF-??B expression and increasing Nrf2 expression in the brain of diabetic rats. 相似文献
4.
Revealing organizational principles of biological networks is an important goal of systems biology. In this study, we sought to analyze the dynamic organizational principles within the protein interaction network by studying the characteristics of individual neighborhoods of proteins within the network based on their gene expression as well as protein-protein interaction patterns. By clustering proteins into distinct groups based on their neighborhood gene expression characteristics, we identify several significant trends in the dynamic organization of the protein interaction network. We show that proteins with distinct neighborhood gene expression characteristics are positioned in specific localities in the protein interaction network thereby playing specific roles in the dynamic network connectivity. Remarkably, our analysis reveals a neighborhood characteristic that corresponds to the most centrally located group of proteins within the network. Further, we show that the connectivity pattern displayed by this group is consistent with the notion of “rich club connectivity” in complex networks. Importantly, our findings are largely reproducible in networks constructed using independent and different datasets. 相似文献
5.
Emin Oguzhan Oguz Hayati Yuksel Yasar Enli A. Cevik Tufan Gunfer Turgut 《Biological trace element research》2010,133(3):335-341
Copper is an essential trace element that is extremely toxic to organisms and organs at high doses. We have investigated the
histological and biochemical effects of a toxic dose of copper sulfate on the liver of term Ross broiler chicks. Fertilized
eggs were divided into three groups: experimental, injected with 50 mcg/0.1 ml copper sulfate in the air chambers on day 1;
sham, injected with 0.1 ml saline; and control, no injection. Term chicks were killed and their livers investigated histologically,
with hematoxylin–eosin-stained sections examined under light microscopy, and biochemically, for malondialdehyde and glutathione
levels. Histological examinations showed copper-treated samples with granular degeneration and necrosis of hepatocytes and
impairment to the cell lining of the remark cords. The samples had a congestive appearance, with blood in the vena centralis
and sinusoids, slight connective tissue increase, and lymphocyte infiltration. Control and sham group sections had normal
appearances. As oxidative damage parameters, in the copper-treated group, malondialdehyde levels were increased and glutathione
levels decreased. In the sham and control groups, there were no significant differences. At this toxic dose, copper sulfate
shows oxidative damage according to the histology of term chick liver that are confirmed biochemically by the changes in malondialdehyde
and glutathione levels. 相似文献
6.
Ulkan Kilic Ozlem Gok Ufuk Erenberk Mehmet Rusen Dundaroz Emel Torun Yasar Kucukardali Birsen Elibol-Can Omer Uysal Tolga Dundar 《PloS one》2015,10(3)
Aging is defined as the accumulation of progressive organ dysfunction. Controlling the rate of aging by clarifying the complex pathways has a significant clinical importance. Nowadays, sirtuins have become famous molecules for slowing aging and decreasing age-related disorders. In the present study, we analyzed the SIRT1 gene polymorphisms (rs7895833 A>G, rs7069102 C>G and rs2273773 C>T) and its relation with levels of SIRT1, eNOS, PON-1, cholesterol, TAS, TOS, and OSI to demonstrate the association between genetic variation in SIRT1 and phenotype at different ages in humans. We observed a significant increase in the SIRT1 level in older people and found a significant positive correlation between SIRT1 level and age in the overall studied population. The oldest people carrying AG genotypes for rs7895833 have the highest SIRT1 level suggesting an association between rs7895833 SNP and lifespan longevity. Older people have lower PON-1 levels than those of adults and children which may explain the high levels of SIRT1 protein as a compensatory mechanism for oxidative stress in the elderly. The eNOS protein level was significantly decreased in older people as compared to adults. There was no significant difference in the eNOS level between older people and children. The current study is the first to demonstrate age-related changes in SIRT1 levels in humans and it is important for a much better molecular understanding of the role of the longevity gene SIRT1 and its protein product in aging. It is also the first study presenting the association between SIRT1 expression in older people and rs7895833 in SIRT1 gene. 相似文献
7.
Adam Ostrowski Mehmet Gundogdu Andrew T. Ferenbach Andrey A. Lebedev Daan M. F. van Aalten 《The Journal of biological chemistry》2015,290(51):30291-30305
Post-translational modification of proteins is a ubiquitous mechanism of signal transduction in all kingdoms of life. One such modification is addition of O-linked N-acetylglucosamine to serine or threonine residues, known as O-GlcNAcylation. This unusual type of glycosylation is thought to be restricted to nucleocytoplasmic proteins of eukaryotes and is mediated by a pair of O-GlcNAc-transferase and O-GlcNAc hydrolase enzymes operating on a large number of substrate proteins. Protein O-GlcNAcylation is responsive to glucose and flux through the hexosamine biosynthetic pathway. Thus, a close relationship is thought to exist between the level of O-GlcNAc proteins within and the general metabolic state of the cell. Although isolated apparent orthologues of these enzymes are present in bacterial genomes, their biological functions remain largely unexplored. It is possible that understanding the function of these proteins will allow development of reductionist models to uncover the principles of O-GlcNAc signaling. Here, we identify orthologues of both O-GlcNAc cycling enzymes in the genome of the thermophilic eubacterium Thermobaculum terrenum. The O-GlcNAcase and O-GlcNAc-transferase are co-expressed and, like their mammalian orthologues, localize to the cytoplasm. The O-GlcNAcase orthologue possesses activity against O-GlcNAc proteins and model substrates. We describe crystal structures of both enzymes, including an O-GlcNAcase·peptide complex, showing conservation of active sites with the human orthologues. Although in vitro activity of the O-GlcNAc-transferase could not be detected, treatment of T. terrenum with an O-GlcNAc-transferase inhibitor led to inhibition of growth. T. terrenum may be the first example of a bacterium possessing a functional O-GlcNAc system. 相似文献
8.
9.
Different types of genetic and epigenetic changes are associated with HNSCC. The molecular mechanisms of HNSCC carcinogenesis are still undergoing intensive investigation. WWOX gene expression is altered in many cancers and in a recent work reduced WWOX expression has been associated with miR-134 expression in HNSCC. In this study we investigated the WWOX messenger RNA expression levels in association with the promoter methylation of the WWOX gene and miR-134 expression levels in 80 HNSCC tumor and non-cancerous tissue samples. Our results show that WWOX expression is down-regulated especially in advanced-stage tumor samples or in tumors with SCC. This down-regulation was associated with methylation of the WWOX promoter region but not with miR-134 expression. There was an inverse correlation between the expression level and promoter methylation. We also analyzed whole exons and exon/intron boundries of the WWOX gene by direct sequencing. In our study group we observed 10 different alterations in the coding sequences and 18 different alterations in the non-coding sequences of the WWOX gene in HNSCC tumor samples. These results indicate that the WWOX gene can be functionally inactivated by promoter methylation, epigenetically or by mutations affecting the sequences coding for the enzymatic domain of the gene, functionally. We conclude that inactivation of WWOX gene contributes to the progression of HNSCC. 相似文献
10.
Jafar Rezaie Reza Rahbarghazi Milad Pezeshki Mahdi Mazhar Farshid Yekani Majid Khaksar Elhameh Shokrollahi Hassan Amini Shahriar Hashemzadeh Sadiye Emel Sokullu Mehmet Tokac 《Journal of cellular physiology》2019,234(12):21732-21745
Extracellular vesicles (EVs) are nano-sized vesicles, released from many cell types including cardiac cells, have recently emerged as intercellular communication tools in cell dynamics. EVs are an important mediator of signaling within cells that influencing the functional behavior of the target cells. In heart complex, cardiac cells can easily use EVs to transport bioactive molecules such as proteins, lipids, and RNAs to the regulation of neighboring cell function. Cross-talk between intracardiac cells plays pivotal roles in the heart homeostasis and in adaptive responses of the heart to stress. EVs were released by cardiomyocytes under baseline conditions, but stress condition such as hypoxia intensifies secretome capacity. EVs secreted by cardiac progenitor cells and cardiosphere-derived cells could be pinpointed as important mediators of cardioprotection and cardiogenesis. Furthermore, EVs from many different types of stem cells could potentially exert a therapeutic effect on the damaged heart. Recent evidence shows that cardiac-derived EVs are rich in microRNAs, suggesting a key role in the controlling of cellular processes. EVs harboring exosomes may be clinically useful in cell-free therapy approaches and potentially act as prognosis and diagnosis biomarkers of cardiovascular diseases. 相似文献