全文获取类型
收费全文 | 6716篇 |
免费 | 601篇 |
国内免费 | 3篇 |
专业分类
7320篇 |
出版年
2023年 | 37篇 |
2022年 | 74篇 |
2021年 | 159篇 |
2020年 | 72篇 |
2019年 | 123篇 |
2018年 | 139篇 |
2017年 | 113篇 |
2016年 | 197篇 |
2015年 | 341篇 |
2014年 | 437篇 |
2013年 | 534篇 |
2012年 | 578篇 |
2011年 | 572篇 |
2010年 | 365篇 |
2009年 | 341篇 |
2008年 | 444篇 |
2007年 | 428篇 |
2006年 | 419篇 |
2005年 | 386篇 |
2004年 | 341篇 |
2003年 | 317篇 |
2002年 | 305篇 |
2001年 | 44篇 |
2000年 | 52篇 |
1999年 | 71篇 |
1998年 | 63篇 |
1997年 | 42篇 |
1996年 | 34篇 |
1995年 | 36篇 |
1994年 | 30篇 |
1993年 | 28篇 |
1992年 | 21篇 |
1991年 | 15篇 |
1990年 | 14篇 |
1989年 | 17篇 |
1988年 | 9篇 |
1987年 | 18篇 |
1986年 | 16篇 |
1985年 | 9篇 |
1983年 | 12篇 |
1981年 | 3篇 |
1980年 | 13篇 |
1979年 | 7篇 |
1978年 | 8篇 |
1977年 | 9篇 |
1975年 | 5篇 |
1974年 | 4篇 |
1972年 | 2篇 |
1970年 | 2篇 |
1965年 | 2篇 |
排序方式: 共有7320条查询结果,搜索用时 15 毫秒
21.
In vivo importance of homologous recombination DNA repair for mouse neural stem and progenitor cells
Rousseau L Etienne O Roque T Desmaze C Haton C Mouthon MA Bernardino-Sgherri J Essers J Kanaar R Boussin FD 《PloS one》2012,7(5):e37194
We characterized the in vivo importance of the homologous recombination factor RAD54 for the developing mouse brain cortex in normal conditions or after ionizing radiation exposure. Contrary to numerous homologous recombination genes, Rad54 disruption did not impact the cortical development without exogenous stress, but it dramatically enhanced the radiation sensitivity of neural stem and progenitor cells. This resulted in the death of all cells irradiated during S or G2, whereas the viability of cells irradiated in G1 or G0 was not affected by Rad54 disruption. Apoptosis occurred after long arrests at intra-S and G2/M checkpoints. This concerned every type of neural stem and progenitor cells, showing that the importance of Rad54 for radiation response was linked to the cell cycle phase at the time of irradiation and not to the differentiation state. In the developing brain, RAD54-dependent homologous recombination appeared absolutely required for the repair of damages induced by ionizing radiation during S and G2 phases, but not for the repair of endogenous damages in normal conditions. Altogether our data support the existence of RAD54-dependent and -independent homologous recombination pathways. 相似文献
22.
Bottone MG Soldani C Tognon G Gorrini C Lazzè MC Brison O Ciomei M Pellicciari C Scovassi AI 《Experimental cell research》2003,290(1):49-59
Paclitaxel affects microtubule stability by binding to beta-tubulin, thus leading to cell accumulation in the G(2)/M phase, polyploidization, and apoptosis. Because both cell proliferation and apoptosis could be somehow regulated by the protooncogene c-myc, in this work we have investigated whether the c-myc amplification level could modulate the multiple effects of paclitaxel. To this aim, paclitaxel was administered to SW613-12A1 and -B3 human colon carcinoma cell lines (which are characterized by a high and low c-myc endogenous amplification level, respectively), and to the B3mycC5 cell line, with an enforced exogenous expression of c-myc copies. In this experimental system, we previously demonstrated that a high endogenous/exogenous level of amplification of c-myc enhances serum deprivation- and DNA damage-induced apoptosis. Accordingly, the present results indicate that a high c-myc amplification level potentiates paclitaxel cytotoxicity, confers a multinucleated phenotype, and promotes apoptosis to a great extent, thus suggesting that c-myc expression level is relevant in modulating the cellular responses to paclitaxel. We have recently shown in HeLa cells that the phosphorylated form of c-Myc accumulates in the nucleus, as distinct nucleolar and extranucleolar spots; here, we demonstrated that, after the treatment with paclitaxel, phosphorylated c-Myc undergoes redistribution, becoming diffused in the nucleoplasm. 相似文献
23.
24.
A novel procedure for genotyping of single nucleotide polymorphisms in trisomy with genomic DNA and the invader assay 下载免费PDF全文
Individuals with trisomy 21 display complex phenotypes with differing degrees of severity. Numerous reliable methods have been established to diagnose the initial trisomy in these patients, but the identification and characterization of the genetic basis of the phenotypic variation in individuals with trisomy remains challenging. To date, methods that can accurately determine genotypes in trisomic DNA samples are expensive, require specialized equipment and complicated analyses. Here we report proof-of-concept results for an Invader® assay-based genotyping procedure that can determine SNP genotypes in trisomic genomic DNA samples in a simple and cost-effective manner. The procedure requires only two experimental steps: a real-time measurement of the fluorescent Invader® signal and analysis with a specifically designed clustering algorithm. The approach was tested using genomic DNA samples from 23 individuals with trisomy 21, and results were compared to genotypes previously determined with pyrosequencing. Additional assays for 15 SNPs were tested in a set of 21 DNA samples to assess assay performance. Our method successfully identified the correct SNP genotypes for the trisomic genomic DNA samples tested, and thus provides an alternative to determine SNP genotypes in trisomic DNA samples for subsequent association studies in patients with Down syndrome and other trisomies. 相似文献
25.
26.
Internal ribosome entry site structural motifs conserved among mammalian fibroblast growth factor 1 alternatively spliced mRNAs 下载免费PDF全文
Martineau Y Le Bec C Monbrun L Allo V Chiu IM Danos O Moine H Prats H Prats AC 《Molecular and cellular biology》2004,24(17):7622-7635
Fibroblast growth factor 1 (FGF-1) is a powerful angiogenic factor whose gene structure contains four promoters, giving rise to a process of alternative splicing resulting in four mRNAs with alternative 5' untranslated regions (5' UTRs). Here we have identified, by using double luciferase bicistronic vectors, the presence of internal ribosome entry sites (IRESs) in the human FGF-1 5' UTRs, particularly in leaders A and C, with distinct activities in mammalian cells. DNA electrotransfer in mouse muscle revealed that the IRES present in the FGF-1 leader A has a high activity in vivo. We have developed a new regulatable TET OFF bicistronic system, which allowed us to rule out the possibility of any cryptic promoter in the FGF-1 leaders. FGF-1 IRESs A and C, which were mapped in fragments of 118 and 103 nucleotides, respectively, are flexible in regard to the position of the initiation codon, making them interesting from a biotechnological point of view. Furthermore, we show that FGF-1 IRESs A of murine and human origins show similar IRES activity profiles. Enzymatic and chemical probing of the FGF-1 IRES A RNA revealed a structural domain conserved among mammals at both the nucleotide sequence and RNA structure levels. The functional role of this structural motif has been demonstrated by point mutagenesis, including compensatory mutations. These data favor an important role of IRESs in the control of FGF-1 expression and provide a new IRES structural motif that could help IRES prediction in 5' UTR databases. 相似文献
27.
Jérôme Dumur Gérard Branlard Anne-Marie Tanguy Mireille Dardevet Olivier Coriton Virginie Huteau Jocelyne Lemoine Joseph Jahier 《Planta》2009,231(1):57-65
In an attempt to improve the bread-making quality within hexaploid wheat by elaborating novel high-molecular weight glutenin
subunits (HMW-GS) combinations useful in wheat-breeding programmes, a 1A chromosome fragment carrying the Glu-A1 locus encoding the subunit Ax2*, was translocated to the long arm of chromosome 1D. The partially isohomoeoallelic line,
designated RR239, had a meiotic behaviour as regular as cv. Courtot. It was characterised using genomic in situ hybridization
and microsatellite markers as well as biochemical and proteomic approaches. The translocated 1D chromosome had an interstitial
1AL segment representing in average 30% of the recombinant arm length that was confirmed by molecular analysis. The genetic
length of the removed segment in chromosome 1DL was estimated to be at least 51 cM, and that of the interstitial 1AL translocation
to be at least 33 cM. Proteome analysis performed on total endosperm proteins revealed variation in amounts, 8 spots and 1
spot being up- and downregulated, respectively. Quantitative variations in HMW-GS were observed for the Glu-A1 (Ax2*) and Glu-B1 (Bx7 + By8) loci in response to duplication of the Glu-A1 locus. 相似文献
28.
29.
30.