全文获取类型
收费全文 | 3399篇 |
免费 | 244篇 |
国内免费 | 129篇 |
专业分类
3772篇 |
出版年
2024年 | 8篇 |
2023年 | 68篇 |
2022年 | 106篇 |
2021年 | 137篇 |
2020年 | 115篇 |
2019年 | 181篇 |
2018年 | 110篇 |
2017年 | 136篇 |
2016年 | 145篇 |
2015年 | 204篇 |
2014年 | 291篇 |
2013年 | 329篇 |
2012年 | 127篇 |
2011年 | 143篇 |
2010年 | 92篇 |
2009年 | 132篇 |
2008年 | 154篇 |
2007年 | 135篇 |
2006年 | 131篇 |
2005年 | 123篇 |
2004年 | 108篇 |
2003年 | 100篇 |
2002年 | 77篇 |
2001年 | 59篇 |
2000年 | 46篇 |
1999年 | 54篇 |
1998年 | 54篇 |
1997年 | 41篇 |
1996年 | 25篇 |
1995年 | 32篇 |
1994年 | 32篇 |
1993年 | 22篇 |
1992年 | 20篇 |
1991年 | 30篇 |
1990年 | 27篇 |
1989年 | 23篇 |
1988年 | 25篇 |
1987年 | 21篇 |
1986年 | 14篇 |
1985年 | 16篇 |
1984年 | 15篇 |
1983年 | 13篇 |
1982年 | 19篇 |
1981年 | 12篇 |
1980年 | 8篇 |
1979年 | 5篇 |
1978年 | 4篇 |
1974年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有3772条查询结果,搜索用时 15 毫秒
11.
The Drosophila brain is generated by a complex series of morphogenetic movements. To better understand brain development and to provide a guide for experimental manipulation of brain progenitors, we created a fate map using photoactivated gene expression to mark cells originating within specific mitotic domains and time-lapse microscopy to dynamically monitor their progeny. We show that mitotic domains 1, 5, and 9 give rise to discrete cell populations within specific regions of the brain. Two novel observations were that the antennal sensory system, composed of four disparate cell clusters, arose from mitotic domain 5 and that mitotic domain B produced glial cells, while neurons were produced from mitotic domains 1, 5, and 9. Time-lapse analysis of marked cells showed complex mitotic and migratory patterns for cells derived from these mitotic domains. Photoactivated gene expression was also used either to kill, to induce ectopic divisions, or to alter cell fate. This revealed that deficits were not repopulated, while ectopic cells were removed and extra glia were tolerated. 相似文献
12.
We measured single strand breaks (SSB) in pancreas DNA produced by N-nitrosobis(2-oxopropyl)amine (BOP) in hamsters fed purified diets containing added sodium selenite (Se) at 0.0, 0.1 and 5.0 ppm. There were fewer SSB in those given the 5.0 ppm Se diet throughout the experiment. One hour after dosing with BOP (20 mg/kg), there were 2.26 ± 0.47, 2.83 ± 0.43 and 1.74 ± 0.43 SSB per 108 daltons (mean ± S.E.M.) respectively in the three groups. The SSB were repaired faster in the 5.0 ppm Se-fed group. The approximate half-lives of the SSB were 33, 30 and 8 days, respectively. In the hamsters fed 5.0 ppm Se there was a small, statistically significant increase in pancreatic DNA synthesis. Autoradiographic analysis indicated that this was repair synthesis. In a second experiment, hamsters were fed one of the three diets prior to and for 2 days after administration of a single dose of BOP (20 mg/kg). They were then fed the 5.0 ppm Se diet for 5 days. The number of SSB was compared with those in hamsters fed their original diet for 7 days after BOP dosing. There was a statistically significant difference in the number of SSB in the hamsters fed 0.1 ppm Se before and for 2 days after BOP. In these hamsters there were 1.21 ± 0.24 SSB per 108 daltons compared with 3.19 ± 0.4 (mean ± S.E.M.). These results suggest high levels of dietary Se stimulate the repair of carcinogen-induced DNA damage. 相似文献
13.
Apurinic/apyrimidinic (AP or abasic) sites are among the most abundant DNA lesions. Numerous proteins within different organisms ranging from bacteria to human have been demonstrated to react with AP sites to form covalent Schiff base DNA–protein cross-links (DPCs). These DPCs are unstable due to their spontaneous hydrolysis, but the half-lives of these cross-links can be as long as several hours. Such long-lived DPCs are extremely toxic due to their large sizes, which physically block DNA replication. Therefore, these adducts must be promptly eradicated to maintain genome integrity. Herein, we used in vitro reconstitution experiments with chemically synthesized, stable, and site-specific Schiff base AP-peptide/protein cross-link analogs to demonstrate for the first time that this type of DPC can be repaired by Escherichia coli (E. coli) long-patch base excision repair. We demonstrated that the repair process requires a minimum of three enzymes and five consecutive steps, including: (1) 5′-DNA strand incision of the DPC by endonuclease IV; (2 to 4) strand-displacement DNA synthesis, removal of the 5′-deoxyribose phosphate-peptide/protein adduct-containing flap, and gap-filling DNA synthesis by DNA polymerase I; and (5) strand ligation by a ligase. We further demonstrated that endonuclease IV plays a major role in incising an AP-peptide cross-link within E. coli cell extracts. We also report that eradicating model AP-protein (11.2–36.1 kDa) DPCs is less efficient than that of an AP-peptide10mer cross-link, supporting the emerging model that proteolysis is likely required for efficient DPC repair. 相似文献
14.
Along Zhao Leilei Yang Kui Ma Mengli Sun Lei Li Jin Huang 《Cell cycle (Georgetown, Tex.)》2016,15(5):644-653
It has been reported that Wnt/β-catenin is critical for dedifferentiation of differentiated epidermal cells. Cyclin D1 (CCND1) is a β-catenin target gene. In this study, we provide evidence that overexpression of CCND1 induces reprogramming of epidermal cells into stem cell-like cells. After introducing CCND1 gene into differentiated epidermal cells, we found that the large flat-shaped cells with a small nuclear-cytoplasmic ratio changed into small round-shaped cells with a large nuclear-cytoplasmic ratio. The expressions of CK10, β1-integrin, Oct4 and Nanog in CCND1 induced cells were remarkably higher than those in the control group (P < 0.01). In addition, the induced cells exhibited a high colony-forming ability and a long-term proliferative potential. When the induced cells were implanted into a wound of laboratory animal model, the wound healing was accelerated. These results suggested that overexpression of CCND1 induced the reprogramming of differentiated epidermal cells into stem cell-like cells. This study may also offer a new approach to yield epidermal stem cells for wound repair and regeneration. 相似文献
15.
The functional loss that often follows injury of the mammalian CNS has been attributed not only to the immediate neural loss, but also to secondary neuronal degeneration caused by toxic biochemical mediators in the environment of the injured nerve. We report here that a high thrombin content, produced as a result of injury-induced activation of prothrombin, appears to be an important mediator of secondary damage. Measurement of post-traumatic neuronal survival in vivo revealed that post-traumatic local application of the thrombin inhibitor N-alpha-(2-naphthylsulphonylglycyl)-4-(D,L)-amidinophenylalanine piperidide acetate in the rat optic nerve subjected to mild partial crush injury left twice as many retinal ganglion cells with functioning axons as in controls. Thus, by readjusting thrombin activity, thereby possibly obtaining a moderate post-traumatic increase and thus gaining the benefit of thrombin without its toxic effects, it may be possible to create an environment that is more favourable for post-traumatic survival. 相似文献
16.
Brunner S Herndler-Brandstetter D Arnold CR Wiegers GJ Villunger A Hackl M Grillari J Moreno-Villanueva M Bürkle A Grubeck-Loebenstein B 《Aging cell》2012,11(4):579-587
The life-long homeostasis of memory CD8(+) T cells as well as persistent viral infections have been shown to facilitate the accumulation of highly differentiated CD8(+) CD28(-) T cells, a phenomenon that has been associated with an impaired immune function in humans. However, the molecular mechanisms regulating homeostasis of CD8(+) CD28(-) T cells have not yet been elucidated. In this study, we demonstrate that the miR-23~24~27 cluster is up-regulated during post-thymic CD8(+) T-cell differentiation in humans. The increased expression of miR-24 in CD8(+) CD28(-) T cells is associated with decreased expression of the histone variant H2AX, a protein that plays a key role in the DNA damage response (DDR). Following treatment with the classic chemotherapeutic agent etoposide, a topoisomerase II inhibitor, apoptosis was increased in CD8(+) CD28(-) when compared to CD8(+) CD28(+) T cells and correlated with an impaired DDR in this cell type. The reduced capacity of CD8(+) CD28(-) T cell to repair DNA was characterized by the automated fluorimetric analysis of DNA unwinding (FADU) assay as well as by decreased phosphorylation of H2AX at Ser139, of ATM at Ser1981, and of p53 at Ser15. Interleukin (IL)-15 could prevent etoposide-mediated apoptosis of CD8(+) CD28(-) T cells, suggesting a role for IL-15 in the survival and the age-dependent accumulation of CD8(+) CD28(-) T cells in humans. 相似文献
17.
Homograft or allograft tissue has been available for use as replacement for diseased valves or reconstruction of major vessels for decades. However, with respect to replacement of diseased valvular tissue the search for the ideal valve still continues. In this review we will discuss the clinical indications, surgical techniques, and outcome of aortic homografts. 相似文献
18.
沉默交配型信息调节因子2同源蛋白1(silent mating type information regulation 2 homolog 1,Sirt1)是哺乳动物中与酵母沉默信息调节蛋白2(silencing information regulator 2,Sir2)高度同源的蛋白质,它是一种依赖NAD+的III类组蛋白去乙酰化酶(HDAC III),在细胞分化、衰老、凋亡、DNA损伤修复、能量及内分泌代谢调节中起重要作用,同时在基因沉默、表观遗传学修饰、转录调控及信号转导调节中发挥重要的生物学功能。本文对其近年的研究进展做一概述。 相似文献
19.
20.