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   1154篇
  免费   26篇
  国内免费   2篇
  1182篇
  2024年   12篇
  2023年   18篇
  2022年   33篇
  2021年   41篇
  2020年   28篇
  2019年   39篇
  2018年   49篇
  2017年   25篇
  2016年   49篇
  2015年   65篇
  2014年   78篇
  2013年   70篇
  2012年   99篇
  2011年   96篇
  2010年   58篇
  2009年   33篇
  2008年   70篇
  2007年   43篇
  2006年   41篇
  2005年   42篇
  2004年   35篇
  2003年   28篇
  2002年   16篇
  2001年   11篇
  2000年   11篇
  1999年   9篇
  1997年   2篇
  1996年   1篇
  1995年   4篇
  1994年   4篇
  1993年   2篇
  1992年   5篇
  1991年   9篇
  1990年   4篇
  1989年   7篇
  1988年   5篇
  1987年   6篇
  1986年   5篇
  1985年   6篇
  1984年   5篇
  1983年   4篇
  1982年   2篇
  1981年   1篇
  1979年   3篇
  1975年   2篇
  1972年   1篇
  1968年   1篇
  1966年   1篇
  1965年   1篇
  1964年   1篇
排序方式: 共有1182条查询结果,搜索用时 0 毫秒
1.
    
A set of novel 6-substituted orvinols was synthesized and pharmacologically characterized in order to explore the effect of the polarity and steric effects of these new moieties on the opioid activity. It was revealed that longer 6-O-alkyl chains led to increased agonistic activities, while the lack of C6-etheral oxygen gave rise to an antagonistic profile at the opioid receptors in the mouse ileum.  相似文献   
2.
    
The biological influence of radiation on living matter has been studied for years; however, several questions about the detailed mechanism of radiation damage formation remain largely unanswered. Among all biomolecules exposed to radiation, DNA plays an important role because any damage to its molecular structure can affect the whole cell and may lead to chromosomal rearrangements resulting in genomic instability or cell death. To identify and characterize damage induced in the DNA sugar-phosphate backbone, in this work we performed x-ray absorption spectroscopy at the P K-edge on DNA irradiated with either UVA light or protons. By combining the experimental results with theoretical calculations, we were able to establish the types and relative ratio of lesions produced by both UVA and protons around the phosphorus atoms in DNA.  相似文献   
3.
4.
    

Background

The zebrafish is an increasingly popular model for studying many aspects of biology. Recently, ztert, the zebrafish homolog of the mammalian telomerase gene has been cloned and sequenced. In contrast to humans, it has been shown that the zebrafish maintains telomerase activity for much of its adult life and has remarkable regenerative capacity. To date, there has been no longitudinal study to assess whether this retention of telomerase activity equates to the retention of chromosome telomere length through adulthood.

Methodology/Principal Findings

We have systematically analyzed individual organs of zebrafish with regard to both telomere length and telomerase activity at various time points in its adult life. Heart, gills, kidney, spleen, liver, and intestine were evaluated at 3 months, 6 months, 9 months, and 2 years of age by Southern blot analysis. We found that telomeres do not appreciably shorten throughout the lifespan of the zebrafish in any organ. In addition, there was little difference in telomere lengths between organs. Even when cells were under the highest pressure to divide after fin-clipping experiments, telomere length was unaffected. All aged (2 year old) tissues examined also expressed active amounts of telomerase activity as assessed by TRAP assay.

Conclusions/Significance

In contrast to several other species including humans, the retention of lifelong telomerase and telomeres, as we have reported here, would be necessary in the zebrafish to maintain its tremendous regenerative capacity. The ongoing study of the zebrafish''s ability to maintain telomerase activity may be helpful in unraveling the complexity involved in the maintenance (or lack thereof) of telomeres in other species such the mouse or human.  相似文献   
5.
6.
  总被引:4,自引:0,他引:4  
The development of lymphoid organs requires membrane-bound lymphotoxin (LT), a heterotrimer containing LTalpha and LTbeta, but the effects of LT on T cell function have not been characterized extensively. Upon TCR cross-linking in vitro, splenocytes from both LTalpha-/- and LTbeta-/- mice failed to produce IL-4 and IL-10 due to a reduction in NK T cells. Concordantly, LTalpha-/- and LTbeta-/- mice did not respond to the lipoglycan alpha-galactosylceramide, which is presented by mouse CD1 to Valpha14+ NK T cells. Interestingly, both populations of NK T cells, including those that are mouse CD1 dependent and alpha-galactosylceramide reactive and those that are not, were affected by disruption of the LTalpha and LTbeta genes. NK T cells were not affected, however, in transgenic mice in which LT signaling is blocked, beginning on day 3 after birth, by expression of a soluble decoy LTbeta receptor. This suggests that membrane-bound LT is critical for NK T cells early in ontogeny, but not for the homeostasis of mature cells.  相似文献   
7.
The mitotic checkpoint ensures proper chromosome segregation by monitoring two critical events during mitosis. One is kinetochore attachment to the mitotic spindle, and the second is the alignment of chromosomes at the metaphase plate, resulting in tension across sister kinetochores (reviewed in [1, 2]). Mitotic-checkpoint proteins are known to accumulate at unaligned chromosomes that have not achieved proper kinetochore-microtubule attachments or established an adequate level of tension across sister kinetochores. Here, we report that hZW10 and hROD, two components of the evolutionarily conserved RZZ complex, accumulate at kinetochores in response to the loss of tension. By using live-cell imaging and FRAP, we showed that the accumulation of hZW10 at tensionless kinetochores stems from a 4-fold reduction of kinetochore turnover rate. We also found that cells lacking hZW10 escape loss-of-tension-induced mitotic-checkpoint arrest more rapidly than those arrested in response to the lack of kinetochore-microtubule attachments. Furthermore, we show that pharmacological inhibition of Aurora B kinase activity with ZM447439 in the absence of tension, but not in the absence of kinetochore-microtubule attachments, results in the loss of hZW10, hROD, and hBub1 from kinetochores. We therefore conclude that Aurora B kinase activity is required for the accumulation of tension-sensitive mitotic-checkpoint components, such as hZW10 and hROD, in order to maintain mitotic-checkpoint arrest.  相似文献   
8.
9.
Histone acetylation and deacetylation participate in the epigenetic regulation of gene expression. In this paper, we demonstrate that pre-treatment with the histone deacetylation inhibitor trichostatin A (TSA) enhances histone acetylation in primary cortical neurons and protects against oxygen/glucose deprivation, a model for ischaemic cell death in vitro. The actin-binding protein gelsolin was identified as a mediator of neuroprotection by TSA. TSA enhanced histone acetylation of the gelsolin promoter region, and up-regulated gelsolin messenger RNA and protein expression in a dose- and time-dependent manner. Double-label confocal immunocytochemistry visualized the up-regulation of gelsolin and histone acetylation within the same neuron. Together with gelsolin up-regulation, TSA pre-treatment decreased levels of filamentous actin. The neuroprotective effect of TSA was completely abolished in neurons lacking gelsolin gene expression. In conclusion, we demonstrate that the enhancement of gelsolin gene expression correlates with neuroprotection induced by the inhibition of histone deacetylation.  相似文献   
10.
A fossil tree was discovered during the 16th century at Jáchymov (Bohemia). The wood was first named by Unger, in 1842, Ulminium diluviale. But it belongs to the Lauraceae family and Felix, in 1883, named it Laurinoxylon diluviale. The authors give the history and the geological setting of the area and describe the anatomy of the wood. The diagnosis of the genus Laurinoxylon Felix, 1883. is emended as follows: heteroxylous fossil wood with average sized solitary vessels or in radial groups; perforation plates simple and sometimes scalariform; intervascular pits alternate and moderately large; thyloses present. Paratracheal parenchyma. Uni to five seriate rays, slightly heterocellular and less than 1 mm high; ray-vessel pits large often stretched. Libriform or with radial pits fibres. Oil cells or mucilage (idioblasts) present. The diagnosis of the species Laurinoxylon diluviale (Unger) Felix, 1883. is also emended. Heteroxylous fossil wood with distinct growth rings; late wood poorly developed with vessels of diameter distinctly smaller as compared to the early wood and with smaller diameter fibres. Diffuse to semiporous vessels, solitary or in radial groups of two to seven , nine to 16 pores/mm2; tangential diameter 100 to 154 μm in early wood and 44 to 72 μm in late wood; vessel length 300 to 550 μm; perforation plates simple and scalariforme (6–12 bars); intervascular pits alternate, rounded (diameter 7–10 μm) or elliptic (long axes × short axes: 10–15 μm × 7–10 μm); thylosis present. Paratracheal parenchyma in more or less complete rows (1–2 cells wide) around the vessels. Heterocellular rays (1–(3) rows of upright cells), of one to five, more frequently three to four cells wide (80%); two to 36 cells high (60 to 820 μm); six to seven rays per tangential millimetre; vessels-rays pits sometimes large, stretched horizontally to vertically. Fibres of 15 to 25 μm in diameter; cell walls of 2–3 μm thick; pits not seen. Oil cells (idioblasts) at the ray margins; 27–60 μm in tangential diameter; 50–80 μm in radial diameter; 72–140 μm high; density of zero to 18 per transversal square millimetres depending on the observed area.  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