全文获取类型
收费全文 | 423篇 |
免费 | 25篇 |
专业分类
448篇 |
出版年
2022年 | 7篇 |
2021年 | 6篇 |
2020年 | 1篇 |
2019年 | 8篇 |
2018年 | 7篇 |
2017年 | 6篇 |
2016年 | 5篇 |
2015年 | 14篇 |
2014年 | 24篇 |
2013年 | 39篇 |
2012年 | 28篇 |
2011年 | 29篇 |
2010年 | 21篇 |
2009年 | 34篇 |
2008年 | 32篇 |
2007年 | 19篇 |
2006年 | 22篇 |
2005年 | 22篇 |
2004年 | 29篇 |
2003年 | 20篇 |
2002年 | 15篇 |
2001年 | 5篇 |
2000年 | 4篇 |
1999年 | 4篇 |
1998年 | 5篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1985年 | 3篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1977年 | 1篇 |
1976年 | 3篇 |
1973年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有448条查询结果,搜索用时 0 毫秒
51.
Assembly of initiation factors on individual replication origins at onset of S phase is crucial for regulation of replication timing and repression of initiation by S-phase checkpoint control. We dissected the process of preinitiation complex formation using a point mutation in fission yeast nda4-108/mcm5 that shows tight genetic interactions with sna41(+)/cdc45(+). The mutation does not affect loading of MCM complex onto origins, but impairs Cdc45-loading, presumably because of a defect in interaction of MCM with Cdc45. In the mcm5 mutant, however, Sld3, which is required for Cdc45-loading, proficiently associates with origins. Origin-association of Sld3 without Cdc45 is also observed in the sna41/cdc45 mutant. These results suggest that Sld3-loading is independent of Cdc45-loading, which is different from those observed in budding yeast. Interestingly, returning the arrested mcm5 cells to the permissive temperature results in immediate loading of Cdc45 to the origin and resumption of DNA replication. These results suggest that the complex containing MCM and Sld3 is an intermediate for initiation of DNA replication in fission yeast. 相似文献
52.
Quantification of mcrA by quantitative fluorescent PCR in sediments from methane seep of the Nankai Trough 总被引:1,自引:0,他引:1
A quantitative fluorogenic PCR method for group-specific methyl coenzyme M reductase subunit A genes (mcrA) from methanotrophic archaea was established and applied to the characterization of microbial communities in anoxic methane seep sediments at the accretionary prism of the Nankai Trough. All of the previously identified subgroups of anaerobic methanotroph (ANME) mcrA genes were detected in the cores up to 25 cm below the seafloor, but distributional patterns of mcrA genes were found to differ according to depth. These findings suggest a distinct distribution of phylogenetically and physiologically diverse methanotrophic archaea that mediate methane oxidation in the anoxic sediments. This quantification method will contribute to future investigations of methanotrophic microbial ecosystems in anoxic marine sediments. 相似文献
53.
Takuro Furusawa Izumi Naka Taro Yamauchi Kazumi Natsuhara Ryosuke Kimura Minato Nakazawa Takafumi Ishida Tsukasa Inaoka Yasuhiro Matsumura Yuji Ataka Nao Nishida Naoyuki Tsuchiya Ryutaro Ohtsuka Jun Ohashi 《Human genetics》2010,127(3):287-294
Various Pacific Island populations have experienced a marked increase in the prevalence of obesity in past decades. This study examined the association of a promoter polymorphism of the leptin gene (LEP), G-2548A (rs7799039), and two non-synonymous single nucleotide polymorphisms of the leptin receptor gene (LEPR), K109R (rs1137100) and Q223R (rs1137101), with body weight, body mass index (BMI) and obesity (BMI ≥ 30) in Pacific Islanders. A total of 745 Austronesian (AN)-speaking participants were analyzed after adjusting for age, gender, and population differences. The results revealed that carriers of the 223Q alleles of LEPR had significantly higher body weight (P = 0.0009) and BMI (P = 0.0022) than non-carriers (i.e., 223R homozygotes); furthermore, the 223Q carriers also had a significantly higher risk of obesity in comparison to non-carriers (P = 0.0222). The other two polymorphisms, G-2548A and K109R, were associated with neither body weight, BMI, nor obesity. The 223Q allele was widely found among the AN-speaking study subjects, thus suggesting that the LEPR Q223R polymorphism is one of the factors contributing to the high prevalence of obesity in the Pacific Island populations. 相似文献
54.
55.
Hwan Su Yoon Takuro Nakayama Adrian Reyes-Prieto Robert A Andersen Sung Min Boo Ken-ichiro Ishida Debashish Bhattacharya 《BMC evolutionary biology》2009,9(1):98
Background
Gaining the ability to photosynthesize was a key event in eukaryotic evolution because algae and plants form the base of the food chain on our planet. The eukaryotic machines of photosynthesis are plastids (e.g., chloroplast in plants) that evolved from cyanobacteria through primary endosymbiosis. Our knowledge of plastid evolution, however, remains limited because the primary endosymbiosis occurred more than a billion years ago. In this context, the thecate "green amoeba" Paulinella chromatophora is remarkable because it very recently (i.e., minimum age of ≈ 60 million years ago) acquired a photosynthetic organelle (termed a "chromatophore"; i.e., plastid) via an independent primary endosymbiosis involving a Prochlorococcus or Synechococcus -like cyanobacterium. All data regarding P. chromatophora stem from a single isolate from Germany (strain M0880/a). Here we brought into culture a novel photosynthetic Paulinella strain (FK01) and generated molecular sequence data from these cells and from four different cell samples, all isolated from freshwater habitats in Japan. Our study had two aims. The first was to compare and contrast cell ultrastructure of the M0880/a and FK01 strains using scanning electron microscopy. The second was to assess the phylogenetic diversity of photosynthetic Paulinella to test the hypothesis they share a vertically inherited plastid that originated in their common ancestor. 相似文献56.
Daisuke Shichi Takuro Arimura Taisuke Ishikawa Akinori Kimura 《The Journal of biological chemistry》2010,285(44):33680-33690
Phosphorylation of myosin regulatory light chain (MLC) plays a regulatory role in muscle contraction, and the level of MLC phosphorylation is balanced by MLC kinase and MLC phosphatase (MLCP). MLCP consists of a catalytic subunit, a large subunit (MYPT1 or MYPT2), and a small subunit. MLCP activity is regulated by phosphorylation of MYPTs, whereas the role of small subunit in the regulation remains unknown. We previously characterized a human heart-specific small subunit (hHS-M21) that increased the sensitivity to Ca2+ in muscle contraction. In this study, we investigated the role of hHS-M21 in the regulation of MLCP phosphorylation. Two isoforms of hHS-M21, hHS-M21A and hHS-M21B, preferentially bound the C-terminal one-third region of MYPT1 and MYPT2, respectively. Amino acid substitutions at a phosphorylation site of MYPT1, Ser-852, impaired the binding of MYPT1 and hHS-M21. The hHS-M21 increased the phosphorylation level of MYPT1 at Thr-696, which was attenuated by Rho-associated kinase (ROCK) inhibitors and small interfering RNAs for ROCK. In addition, hHS-M21 bound ROCK and enhanced the ROCK activity. These findings suggest that hHS-M21 is a heart-specific effector of ROCK and plays a regulatory role in the MYPT1 phosphorylation at Thr-696 by ROCK. 相似文献
57.
58.
Mori T Inamori K Inoue Y Han X Yamanouchi G Niidome T Katayama Y 《Analytical biochemistry》2008,375(2):223-231
We developed a peptide microarray based on surface plasmon resonance (SPR) imaging for monitoring protein kinase activities in cell lysates. The substrate peptides of kinases were tethered to the microarray surface modified with a self-assembled monolayer of an alkanethiol with triethylene glycol terminus to create a low nonspecific binding surface. The phosphorylation of the substrate peptides immobilized on the surface was detected with the following phosphate specific binders by amplifying SPR signals: anti-phosphotyrosine antibody for tyrosine kinases and Phos-tag biotin (a phosphate-specific ligand with biotin tag) for serine/threonine kinases. Using the microarray, 9 kinds of protein kinases were evaluated as a pattern of phosphorylation of 26 kinds of substrate peptides. The pattern was unique for each protein kinase. The microarray could be used to evaluate the inhibitory activities of kinase inhibitors. The microarray was applied successfully for kinase activity monitoring of cell lysates. The chemical stimuli responsive activity changes of protein kinases in cell lysates could also be monitored by the peptide microarray. Thus, the peptide microarray based on SPR imaging would be applicable to cell-based drug discovery, diagnosis using tissue lysates, and biochemical studies to reveal signal transduction pathways. 相似文献
59.
60.
When intact Toxoplasma trophozoites were stained with isotonic alkaline methylene blue solution, the organelles rich in nucleic acid, i.e., nucleus, free and membrane-bound ribosomes appeared as electron dense areas. When the parasites were incubated with the anti-Toxoplasma antibody and the accessory factor, swelling of the surface membrane occurred first, followed by destruction of the inner structures. In the dye test positive parasites, there were no definite organelles recognizable, as there were in the intact parasites. By the negative staining method, holes (defects) with dark central portions were observed on the surface of the parasites treated with the antibody and the accessory factor, the diameter of the holes measuring about 10–11 nm. These holes, which tended to occur in clusters, were each surrounded by a clear ring. 相似文献