全文获取类型
收费全文 | 548篇 |
免费 | 29篇 |
专业分类
577篇 |
出版年
2023年 | 1篇 |
2022年 | 4篇 |
2021年 | 7篇 |
2020年 | 3篇 |
2019年 | 5篇 |
2018年 | 8篇 |
2017年 | 10篇 |
2016年 | 10篇 |
2015年 | 17篇 |
2014年 | 34篇 |
2013年 | 30篇 |
2012年 | 43篇 |
2011年 | 36篇 |
2010年 | 21篇 |
2009年 | 24篇 |
2008年 | 41篇 |
2007年 | 28篇 |
2006年 | 34篇 |
2005年 | 39篇 |
2004年 | 42篇 |
2003年 | 25篇 |
2002年 | 30篇 |
2001年 | 5篇 |
2000年 | 4篇 |
1999年 | 7篇 |
1998年 | 6篇 |
1997年 | 7篇 |
1996年 | 1篇 |
1995年 | 7篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 7篇 |
1991年 | 4篇 |
1990年 | 2篇 |
1989年 | 5篇 |
1988年 | 8篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1973年 | 2篇 |
1968年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有577条查询结果,搜索用时 15 毫秒
61.
Myers' elegant and powerful bit-parallel dynamic programming algorithm for approximate string matching has a restriction that the query length should be within the word size of the computer, typically 64. We propose a modification of Myers' algorithm, in which the modification has a restriction not on the query length but on the maximum number of mismatches (substitutions, insertions, or deletions), which should be less than half of the word size. The time complexity is O(m log |Σ|), where m is the query length and |Σ| is the size of the alphabet Σ. Thus, it is particularly suited for sequences on a small alphabet such as DNA sequences. In particular, it is useful in quickly extending a large number of seed alignments against a reference genome for high-throughput short-read data produced by next-generation DNA sequencers. 相似文献
62.
63.
64.
New findings reveal that, in Caenorhabditis elegans embryos, the centrosome provides signals that induce cell polarization, independently of its function as the microtubule-organizing center. 相似文献
65.
The endoplasmic reticulum (ER)-Golgi sterol transfer activity of oxysterol-binding protein (OSBP) regulates sphingomyelin (SM) synthesis, as well as post-Golgi cholesterol efflux pathways. The phosphorylation and ER-Golgi localization of OSBP are correlated, suggesting this modification regulates the directionality and/or specificity of transfer activity. In this paper, we report that phosphorylation on two serine-rich motifs, S381-S391 (site 1) and S192, S195, S200 (site 2), specifically controls OSBP activity at the ER. A phosphomimetic of the SM/cholesterol-sensitive phosphorylation site 1 (OSBP-S5E) had increased in vitro cholesterol and 25-hydroxycholesterol-binding capacity, and cholesterol extraction from liposomes, but reduced transfer activity. Phosphatidylinositol 4-phosphate (PI(4)P) and cholesterol competed for a common binding site on OSBP; however, direct binding of PI(4)P was not affected by site 1 phosphorylation. Individual site 1 and site 2 phosphomutants supported oxysterol activation of SM synthesis in OSBP-deficient CHO cells. However, a double site1/2 mutant (OSBP-S381A/S3D) was deficient in this activity and was constitutively colocalized with vesicle-associated membrane protein-associated protein A (VAP-A) in a collapsed ER network. This study identifies phosphorylation regulation of sterol and VAP-A binding by OSBP in the ER, and PI(4)P as an alternate ligand that could be exchanged for sterol in the Golgi apparatus. 相似文献
66.
67.
Minehara H Narita A Naka K Tanaka K Chujo M Nagao M Chujo Y 《Bioorganic & medicinal chemistry》2012,20(15):4675-4679
We report the tumor cell-selective prodrugs based on the arsonic acid-presenting iron oxide nanoparticles. We synthesized the well-dispersed nanoparticles having arsonoacetic acid which is composed of the low toxic As(V) form. From the analyses of the reaction products, it is suggested that the reduction by dithiothreitol with arsonoacetic acid and the modified nanoparticles could generate the highly-toxic As(III) species. In the MTT assays, it was found that the cell viabilities of HeLaS3 and especially HepG2 were reduced in the presence of the modified nanoparticles. In contrast, a slight effect on viability was observed with primary mouse hepatocytes. The viabilities showed good agreements with the amounts of intracellular reduced glutathione concentrations. Furthermore, the valid concentrations of the modified nanoparticles for tumor-specific cytotoxicity were similar level in MRI measurements. These results indicate that arsonic acid-presenting nanoparticles should be a good platform for developing highly-sensitive tumor-specific prodrugs. 相似文献
68.
Asako Murayama Nao Sugiyama Seiko Yoshimura Mitsuko Ishihara-Sugano Takahiro Masaki Sulyi Kim Takaji Wakita Shunji Mishiro Takanobu Kato 《PloS one》2012,7(12)
Hepatitis C virus (HCV) cell culture system with JFH-1 strain and HuH-7 cells enabled us to produce infectious HCV particles in vitro, and such system is useful to explore the anti-HCV compounds and to develop the vaccine against HCV. In the present study, we describe the derivation of a cell line that permits improved production of HCV particles. Specifically, we characterized several subclones that were isolated from the original HuH-7 cell line by limiting dilution. These HuH-7 subclones displayed a notable range of HCV production levels following transfection by full-genome JFH-1 RNA. Among these subclones, HuH-7T1 produced HCV more efficiently than other subclones and Huh-7.5.1 that is known to be highly permissive for HCV replication. Upon transfection with full-genome RNA, HCV production was increased ten-fold in HuH-7T1 compared to Huh-7.5.1. This increase in viral production correlated with increased efficiency of intracellular infectious virus production. Furthermore, HCV replication did not induce cell cycle arrest in HuH-7T1, whereas it did in Huh-7.5.1. Consequently, the use of HuH-7T1 as host cells could provide increased population of HCV-positive cells and elevated viral titer. In conclusion, we isolated a HuH-7 subclone, HuH-7T1, that supports efficient HCV production. High efficiency of intracellular infectious virus production and evasion of cell cycle arrest were important for this phenotype. We expect that the use of this cell line will facilitate analysis of the underlying mechanisms for HCV particle assembly and the cell cycle arrest caused by HCV. 相似文献
69.
Microsatellite diversity and crossover regions within homozygous and heterozygous SLA haplotypes of different pig breeds 总被引:2,自引:0,他引:2
Ando A Uenishi H Kawata H Tanaka-Matsuda M Shigenari A Flori L Chardon P Lunney JK Kulski JK Inoko H 《Immunogenetics》2008,60(7):399-407
Our aim was to investigate microsatellite (MS) diversity and find crossover regions at 42 polymorphic MS loci in the swine leukocyte antigen (SLA) genomic region of 72 pigs with different well-defined homozygous and heterozygous SLA haplotypes. We analyzed the genetic polymorphisms of 42 MS markers in 23 SLA homozygous-heterozygous, common pig breeds with 12 SLA serological haplotypes and 49 National Institutes of Health (NIH) and Clawn homozygous-heterozygous miniature pigs with nine SLA serological or genotyped haplotypes including four recombinant haplotypes. In comparing the same and different haplotypes, both haplospecific patterns and allelic variations were observed at the MS loci. Some of the shared haplotype blocks extended over 2 Mb suggesting the existence of strong linkage disequilibrium (LD) in the entire SLA region. Crossover regions were easily defined by the MS markers within the class I and/or III region in the NIH and Clawn recombinant haplotypes. The present haplotype comparison shows that our set of MS markers provides a fast and cost-efficient alternative, or complementary, method to the serological or sequence-based determination of the SLA alleles for the characterization of SLA haplotypes and/or the crossover regions between different haplotypes. 相似文献
70.