全文获取类型
收费全文 | 3472篇 |
免费 | 243篇 |
国内免费 | 129篇 |
专业分类
3844篇 |
出版年
2024年 | 8篇 |
2023年 | 67篇 |
2022年 | 102篇 |
2021年 | 135篇 |
2020年 | 112篇 |
2019年 | 181篇 |
2018年 | 110篇 |
2017年 | 129篇 |
2016年 | 139篇 |
2015年 | 207篇 |
2014年 | 301篇 |
2013年 | 334篇 |
2012年 | 148篇 |
2011年 | 153篇 |
2010年 | 101篇 |
2009年 | 134篇 |
2008年 | 157篇 |
2007年 | 139篇 |
2006年 | 131篇 |
2005年 | 122篇 |
2004年 | 109篇 |
2003年 | 104篇 |
2002年 | 77篇 |
2001年 | 60篇 |
2000年 | 49篇 |
1999年 | 54篇 |
1998年 | 54篇 |
1997年 | 43篇 |
1996年 | 26篇 |
1995年 | 34篇 |
1994年 | 32篇 |
1993年 | 24篇 |
1992年 | 21篇 |
1991年 | 33篇 |
1990年 | 27篇 |
1989年 | 25篇 |
1988年 | 26篇 |
1987年 | 23篇 |
1986年 | 16篇 |
1985年 | 16篇 |
1984年 | 15篇 |
1983年 | 13篇 |
1982年 | 20篇 |
1981年 | 12篇 |
1980年 | 9篇 |
1979年 | 5篇 |
1978年 | 4篇 |
1974年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有3844条查询结果,搜索用时 0 毫秒
101.
《DNA Repair》2019
Poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) acts as a DNA damage sensor. It recognizes DNA damage and facilitates DNA repair by recruiting DNA repair machinery to damage sites. Recent studies reported that PARP-1 also plays an important role in DNA replication by recognizing the unligated Okazaki fragments and controlling the speed of fork elongation. On the other hand, emerging evidence reveals that excessive activation of PARP-1 causes chromatin DNA fragmentation and triggers an intrinsic PARP-1-dependent cell death program designated parthanatos, which can be blocked by genetic deletion or pharmacological inhibition of PARP-1. Therefore, PARP-1 plays an essential role in maintaining genomic stability by either facilitating DNA repair/replication or triggering DNA fragmentation to kill cells. A group of structure-specific nucleases is crucial for executing DNA incision and fragmentation following PARP-1 activation. In this review, we will discuss how PARP-1 coordinates with its associated nucleases to maintain genomic integrity and control the decision of cell life and death. 相似文献
102.
目的:观察生长激素-海藻酸钠-壳聚糖微胶囊促进兔挠骨骨折愈合的作用。方法:实验将新西兰兔80只,在制备新西兰兔右桡骨中段3mm骨缺损模型的基础上,随机分成四组:口服生长激素-海藻酸钠-壳聚糖微胶囊组、皮下注射生长激素组、口服空微胶囊组和生理盐水对照组。实验组口服生长激素-海藻酸钠-壳聚糖微胶囊和皮下注射生长激素,对照组口服空微胶囊。并于术后9、17、30、42d定期HE染色和地衣红染色观察各组的骨折愈合情况。结果:本实验HE染色结果表明,由于在骨缺损部位成纤维细胞产生的大量胶原纤维为基质,形成透明软骨及成骨细胞,骨小梁生长的基础,连接骨痂形成和骨髓腔贯通。而观察到生长激素微胶囊组各期提前生长及改建提前的形态。地衣红染色图像结果分析及直方图的分析表明:生长激素微胶囊组胶原纤维产生促进骨小梁提前形成,进而骨折处骨性骨痂的提前愈合和髓腔的提前贯通。结论:生长激素-海藻酸钠-壳聚糖微胶囊口服能促进骨折修复愈合。 相似文献
103.
Longhou Fangt YiGuo Wang Dan Dut Guang Yang Tim Tak Kwok Siu Kai Kong Benjamin Chen David J Chen Zhengjun Chen 《Cell research》2007,17(6):572-574
The author affiliations were mixed up in the previous published version. The third fund number of National Natural Science Foundation of China in the Acknowledgments was wrong, it should be "30270335". The Shanghai Municipal Council for Science and Technology (No.06DZ22032) was missed in the Acknowledgments. There are some labeling and production errors in Figure 2A, Figure 3B and 3C, Figure 5C, Figure 6B and 6E, Figure 7B and 7D. 相似文献
104.
MRN复合物包括MRE11、NBS1、RAD50,此复合物中的MRE11或NBS1缺失或突变会导致人的共济失调一毛细血管扩张样疾病、Nijmegen断裂综合征。MRN复合物在DNA双链损伤修复、同源重组、非同源重组、端粒长度维持、细胞检验点激活、保证DNA复制的顺利进行,以及维持基因组的稳定性等方面都起到了重要的作用。从以上几个方面简要综述MRN复合物的研究进展。 相似文献
105.
Hsu-Feng Lu Jai-Sing Yang Kuang-Chi Lai Shu-Chun Hsu Shu-Ching Hsueh Yuan-Liang Chen Jo-Hua Chiang Chi-Cheng Lu Chyi Lo Mei-Due Yang Jing-Gung Chung 《Neurochemical research》2009,34(8):1491-1497
Curcumin is reported to be a potent inhibitor of the initiation and promotion of many cancer cells. We investigated to examine
whether or not curcumin induce DNA damage in mouse–rat hybrid retina ganglion cell line N18 cells. The Comet assay showed
that incubation of N18 cells with 10, 25 and 30 μM of curcumin led to a longer DNA migration smear (Comet tail). The DNA gel
electrophoresis showed that 20 μM of curcumin for 24 and 48 h treatment induced DNA damage and fragments in N18 cells. The
real time PCR analysis showed that 20 μM of curcumin for 48 h treatment decreased ATM, ATR, BRCA1, 14-3-3σ, DNA-PK and MGMT
mRNA, and ATM and MGMT mRNA expression were inhibited in a time-dependent manner. Our results indicate that curcumin caused
DNA damage and inhibited DNA repair genes which may be the factors for curcumin-inhibited cell growth.
H.-F. Lu and J.-S. Yang are contributed equally to this study. 相似文献
106.
Andrew J.Parsons Ifty Ahmed Papia Haque Ben Fitzpatrick Muhammad I.K.Niazi Gavin S.Walker Chris D.Rudd 《仿生工程学报(英文版)》2009,6(4):318-323
We investigate high-modulus degradable materials intended to replace metals in biomedical applications.These are typicallycomposites comprising a polylactide(PLA)matrix reinforced with phosphate glass fibres,which provide reinforcementsimilar to E-glass but are entirely degradable in water to produce,principally,calcium phosphate.We have made compositesusing a variety of fibre architectures,from non-woven random mats to unidirectional fibre tapes.Flexural properties in theregion of 30 GPa modulus and 350 MPa strength have been achieved-directly comparable to quoted values for human corticalbone.In collaboration with other groups we have begun to consider the development of foamed systems with structures mimickingcancellous bone and this has shown significant promise.The fibres in these foamed structures provide improved creepresistance and reinforcement of the pore walls.To date the materials have exhibited excellent cellular responses in vitro andfurther studies are due to include consideration of the surface character of the materials and the influence of this on cell interaction,both with the composites and the glass fibres themselves,which show promise as a standalone porous scaffold. 相似文献
107.
Mary C. Andorfer Lindsey R.F. Backman Phoebe L. Li Emily C. Ulrich Catherine L. Drennan 《The Journal of biological chemistry》2021,297(6)
Pyruvate formate-lyase (PFL) is a glycyl radical enzyme (GRE) that converts pyruvate and coenzyme A into acetyl-CoA and formate in a reaction that is crucial to the primary metabolism of many anaerobic bacteria. The glycyl radical cofactor, which is posttranslationally installed by a radical S-adenosyl-L-methionine (SAM) activase, is a simple and effective catalyst, but is also susceptible to oxidative damage in microaerobic environments. Such damage occurs at the glycyl radical cofactor, resulting in cleaved PFL (cPFL). Bacteria have evolved a spare part protein termed YfiD that can be used to repair cPFL. Previously, we obtained a structure of YfiD by NMR spectroscopy and found that the N-terminus of YfiD was disordered and that the C-terminus of YfiD duplicates the structure of the C-terminus of PFL, including a β-strand that is not removed by the oxygen-induced cleavage. We also showed that cPFL is highly susceptible to proteolysis, suggesting that YfiD rescue of cPFL competes with protein degradation. Here, we probe the mechanism by which YfiD can bind and restore activity to cPFL through enzymatic and spectroscopic studies. Our data show that the disordered N-terminal region of YfiD is important for YfiD glycyl radical installation but not for catalysis, and that the duplicate β-strand does not need to be cleaved from cPFL for YfiD to bind. In fact, truncation of this PFL region prevents YfiD rescue. Collectively our data suggest the molecular mechanisms by which YfiD activation is precluded both when PFL is not damaged and when it is highly damaged. 相似文献
108.
Fanconi DNA repair pathway is required for survival and long-term maintenance of neural progenitors 下载免费PDF全文
Sii-Felice K Etienne O Hoffschir F Mathieu C Riou L Barroca V Haton C Arwert F Fouchet P Boussin FD Mouthon MA 《The EMBO journal》2008,27(5):770-781
Although brain development abnormalities and brain cancer predisposition have been reported in some Fanconi patients, the possible role of Fanconi DNA repair pathway during neurogenesis is unclear. We thus addressed the role of fanca and fancg, which are involved in the activation of Fanconi pathway, in neural stem and progenitor cells during brain development and adult neurogenesis. Fanca(-/-) and fancg(-/-) mice presented with microcephalies and a decreased neuronal production in developing cortex and adult brain. Apoptosis of embryonic neural progenitors, but not that of postmitotic neurons, was increased in the neocortex of fanca(-/-) and fancg(-/-) mice and was correlated with chromosomal instability. In adult Fanconi mice, we showed a reduced proliferation of neural progenitor cells related to apoptosis and accentuated neural stem cells exhaustion with ageing. In addition, embryonic and adult Fanconi neural stem cells showed a reduced capacity to self-renew in vitro. Our study demonstrates a critical role for Fanconi pathway in neural stem and progenitor cells during developmental and adult neurogenesis. 相似文献
109.
110.