全文获取类型
收费全文 | 704篇 |
免费 | 48篇 |
出版年
2022年 | 5篇 |
2021年 | 9篇 |
2019年 | 4篇 |
2018年 | 10篇 |
2017年 | 8篇 |
2016年 | 5篇 |
2015年 | 22篇 |
2014年 | 19篇 |
2013年 | 49篇 |
2012年 | 34篇 |
2011年 | 31篇 |
2010年 | 24篇 |
2009年 | 17篇 |
2008年 | 32篇 |
2007年 | 34篇 |
2006年 | 27篇 |
2005年 | 40篇 |
2004年 | 39篇 |
2003年 | 38篇 |
2002年 | 40篇 |
2001年 | 26篇 |
2000年 | 26篇 |
1999年 | 24篇 |
1998年 | 6篇 |
1997年 | 7篇 |
1996年 | 5篇 |
1995年 | 6篇 |
1994年 | 7篇 |
1993年 | 6篇 |
1992年 | 12篇 |
1991年 | 12篇 |
1990年 | 8篇 |
1989年 | 7篇 |
1988年 | 15篇 |
1987年 | 8篇 |
1986年 | 17篇 |
1985年 | 10篇 |
1984年 | 15篇 |
1983年 | 2篇 |
1982年 | 11篇 |
1981年 | 5篇 |
1980年 | 7篇 |
1978年 | 3篇 |
1977年 | 1篇 |
1976年 | 3篇 |
1975年 | 5篇 |
1974年 | 2篇 |
1973年 | 4篇 |
1971年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有752条查询结果,搜索用时 15 毫秒
31.
Kenta Shirasawa Hiroyuki Fukuoka Hiroshi Matsunaga Yuhko Kobayashi Issei Kobayashi Hideki Hirakawa Sachiko Isobe Satoshi Tabata 《DNA research》2013,20(6):593-603
With the aim of understanding relationship between genetic and phenotypic variations in cultivated tomato, single nucleotide polymorphism (SNP) markers covering the whole genome of cultivated tomato were developed and genome-wide association studies (GWAS) were performed. The whole genomes of six tomato lines were sequenced with the ABI-5500xl SOLiD sequencer. Sequence reads covering ∼13.7× of the genome for each line were obtained, and mapped onto tomato reference genomes (SL2.40) to detect ∼1.5 million SNP candidates. Of the identified SNPs, 1.5% were considered to confer gene functions. In the subsequent Illumina GoldenGate assay for 1536 SNPs, 1293 SNPs were successfully genotyped, and 1248 showed polymorphisms among 663 tomato accessions. The whole-genome linkage disequilibrium (LD) analysis detected highly biased LD decays between euchromatic (58 kb) and heterochromatic regions (13.8 Mb). Subsequent GWAS identified SNPs that were significantly associated with agronomical traits, with SNP loci located near genes that were previously reported as candidates for these traits. This study demonstrates that attractive loci can be identified by performing GWAS with a large number of SNPs obtained from re-sequencing analysis. 相似文献
32.
Kenta Shirasawa Kohei Ishii Cholgwang Kim Tomohiro Ban Munenori Suzuki Takashi Ito Toshiya Muranaka Megumi Kobayashi Noriko Nagata Sachiko Isobe Satoshi Tabata 《Molecular breeding : new strategies in plant improvement》2013,31(1):101-110
Capsicum spp. are widely cultivated for use as vegetables and spices. The Kihara Institute for Biological Research, Yokohama City University, Japan, has stocks of approximately 800 lines of Capsicum spp. collected from various regions of Central and South America, the regions of origin for Capsicum spp. In this study, 5,751 primer pairs for simple sequence repeat markers, based on 118,060 publicly available sequences of expressed sequence tags of Capsicum annuum, were designed and subjected to a similarity search against the genomic sequence of tomato, a model Solanaceae species. Nucleotide sequences spanning 2,245 C. annuum markers were successfully mapped onto the tomato genome, and 96 of these, which spanned the entire tomato genome, were selected for further analysis. In genotyping analysis, 60 out of the 77 markers that produced specific DNA amplicons showed polymorphism among the Capsicum lines examined. On the basis of the resulting data, the 192 tested lines were grouped into five main clusters. The additional sequencing analysis of the plastid genes, matK and rbcL, divided the resources into three groups. As a result, 19 marker loci exhibited genotypes specific to species and cluster, suggesting that the DNA markers are useful for species identification. Information on the DNA markers will contribute to Capsicum genetics, genomics, and breeding. 相似文献
33.
Takuya Matsushita Takahisa Tateishi Noriko Isobe Tomomi Yonekawa Ryo Yamasaki Dai Matsuse Hiroyuki Murai Jun-ichi Kira 《PloS one》2013,8(4)
Background
Differences in cytokine/chemokine profiles among patients with neuromyelitis optica (NMO), relapsing remitting multiple sclerosis (RRMS), and primary progressive MS (PPMS), and the relationships of these profiles with clinical and neuroimaging features are unclear. A greater understanding of these profiles may help in differential diagnosis.Methods/Principal Findings
We measured 27 cytokines/chemokines and growth factors in CSF collected from 20 patients with NMO, 26 with RRMS, nine with PPMS, and 18 with other non-inflammatory neurological diseases (OND) by multiplexed fluorescent bead-based immunoassay. Interleukin (IL)-17A, IL-6, CXCL8 and CXCL10 levels were significantly higher in NMO patients than in OND and RRMS patients at relapse, while granulocyte-colony stimulating factor (G-CSF) and CCL4 levels were significantly higher in NMO patients than in OND patients. In NMO patients, IL-6 and CXCL8 levels were positively correlated with disability and CSF protein concentration while IL-6, CXCL8, G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-γ were positively correlated with CSF neutrophil counts at the time of sample collection. In RRMS patients, IL-6 levels were significantly higher than in OND patients at the relapse phase while CSF cell counts were negatively correlated with the levels of CCL2. Correlation coefficients of cytokines/chemokines in the relapse phase were significantly different in three combinations, IL-6 and GM-CSF, G-CSF and GM-CSF, and GM-CSF and IFN-γ, between RRMS and NMO/NMOSD patients. In PPMS patients, CCL4 and CXCL10 levels were significantly higher than in OND patients.Conclusions
Our findings suggest distinct cytokine/chemokine alterations in CSF exist among NMO, RRMS and PPMS. In NMO, over-expression of a cluster of Th17- and Th1-related proinflammatory cytokines/chemokines is characteristic, while in PPMS, increased CCL4 and CXCL10 levels may reflect on-going low grade T cell and macrophage/microglia inflammation in the central nervous system. In RRMS, only a mild elevation of proinflammatory cytokines/chemokines was detectable at relapse. 相似文献34.
35.
Motoshi Kunugi Atsushi Takabayashi Ayumi Tanaka 《The Journal of biological chemistry》2013,288(27):19330-19341
Chlorophyll b is found in photosynthetic prokaryotes and primary and secondary endosymbionts, although their light-harvesting systems are quite different. Chlorophyll b is synthesized from chlorophyll a by chlorophyllide a oxygenase (CAO), which is a Rieske-mononuclear iron oxygenase. Comparison of the amino acid sequences of CAO among photosynthetic organisms elucidated changes in the domain structures of CAO during evolution. However, the evolutionary relationship between the light-harvesting system and the domain structure of CAO remains unclear. To elucidate this relationship, we investigated the CAO structure and the pigment composition of chlorophyll-protein complexes in the prasinophyte Micromonas. The Micromonas CAO is composed of two genes, MpCAO1 and MpCAO2, that possess Rieske and mononuclear iron-binding motifs, respectively. Only when both genes were introduced into the chlorophyll b-less Arabidopsis mutant (ch1-1) was chlorophyll b accumulated, indicating that cooperation between the two subunits is required to synthesize chlorophyll b. Although Micromonas has a characteristic light-harvesting system in which chlorophyll b is incorporated into the core antennas of reaction centers, chlorophyll b was also incorporated into the core antennas of reaction centers of the Arabidopsis transformants that contained the two Micromonas CAO proteins. Based on these results, we discuss the evolutionary relationship between the structures of CAO and light-harvesting systems. 相似文献
36.
Taeko Kimura Koji Tsutsumi Masato Taoka Taro Saito Masami Masuda-Suzukake Koichi Ishiguro Florian Plattner Takafumi Uchida Toshiaki Isobe Masato Hasegawa Shin-ichi Hisanaga 《The Journal of biological chemistry》2013,288(11):7968-7977
Neurodegenerative diseases associated with the pathological aggregation of microtubule-associated protein Tau are classified as tauopathies. Alzheimer disease, the most common tauopathy, is characterized by neurofibrillary tangles that are mainly composed of abnormally phosphorylated Tau. Similar hyperphosphorylated Tau lesions are found in patients with frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) that is induced by mutations within the tau gene. To further understand the etiology of tauopathies, it will be important to elucidate the mechanism underlying Tau hyperphosphorylation. Tau phosphorylation occurs mainly at proline-directed Ser/Thr sites, which are targeted by protein kinases such as GSK3β and Cdk5. We reported previously that dephosphorylation of Tau at Cdk5-mediated sites was enhanced by Pin1, a peptidyl-prolyl isomerase that stimulates dephosphorylation at proline-directed sites by protein phosphatase 2A. Pin1 deficiency is suggested to cause Tau hyperphosphorylation in Alzheimer disease. Up to the present, Pin1 binding was only shown for two Tau phosphorylation sites (Thr-212 and Thr-231) despite the presence of many more hyperphosphorylated sites. Here, we analyzed the interaction of Pin1 with Tau phosphorylated by Cdk5-p25 using a GST pulldown assay and Biacore approach. We found that Pin1 binds and stimulates dephosphorylation of Tau at all Cdk5-mediated sites (Ser-202, Thr-205, Ser-235, and Ser-404). Furthermore, FTDP-17 mutant Tau (P301L or R406W) showed slightly weaker Pin1 binding than non-mutated Tau, suggesting that FTDP-17 mutations induce hyperphosphorylation by reducing the interaction between Pin1 and Tau. Together, these results indicate that Pin1 is generally involved in the regulation of Tau hyperphosphorylation and hence the etiology of tauopathies. 相似文献
37.
Jun-ichi Kanatani Junko Isobe Keiko Kimata Tomoko Shima Miwako Shimizu Fumiaki Kura Tetsutaro Sata Masanori Watahiki 《Applied and environmental microbiology》2013,79(13):3959-3966
We investigated the prevalence of Legionella species isolated from puddles on asphalt roads. In addition, we carried out sequence-based typing (SBT) analysis on the genetic relationship between L. pneumophila serogroup 1 (SG 1) isolates from puddles and from stock strains previously obtained from sputum specimens and public baths. Sixty-nine water samples were collected from puddles on roads at 6 fixed locations. Legionella species were detected in 33 samples (47.8%) regardless of season. Among the 325 isolates from puddles, strains of L. pneumophila SG 1, a major causative agent of Legionnaires'' disease, were the most frequently isolated (n = 62, 19.1%). Sixty-two isolates of L. pneumophila SG 1 from puddles were classified into 36 sequence types (STs) by SBT. ST120 and ST48 were identified as major STs. Environmental ST120 strains from puddles were found for the first time in this study. Among the 14 STs of the clinical isolates (n = 19), 4 STs (n = 6, 31.6%), including ST120, were also detected in isolates from puddles on roads, and the sources of infection in these cases remained unclear. The lag-1 gene, a tentative marker for clinical isolates, was prevalent in puddle isolates (61.3%). Our findings suggest that puddles on asphalt roads serve as potential reservoirs for L. pneumophila in the environment. 相似文献
38.
Tomoya Ogawa Motoshi Yasui Masanao Matsui 《Bioscience, biotechnology, and biochemistry》2013,77(8):1445-1447
The Colletotrichum lagenarium PKS1 gene was expressed in the heterologous fungal host, Aspergillus oryzae, under the starch-inducible α-amylase promoter to identify the direct product of polyketide synthase (PKS) encoded by the PKS1 gene. The main compound produced by an A. oryzae transformant was isolated and characterized to be 1,3,6,8-tetrahydroxynaphthalene (T4HN) as its tetraacetate. Since the PKS1 gene was cloned from C. lagenarium to complement the nonmelanizing albino mutant, T4HN was assumed to be an initial biosynthetic intermediate, and thus the product of the PKS reaction, but had not been isolated from the fungus. The production of T4HN by the PKS1 transformant unambiguously identified the gene to encode a PKS of pentaketide T4HN. In addition, tetraketide orsellinic acid and pentaketide isocoumarin were isolated, the latter being derived from a pentaketide monocyclic carboxylic acid, as by-products of the PKS1 PKS reaction. Production of the pentaketide carboxylic acid provided insights into the mechanism for the PKS1 polyketide synthase reaction to form T4HN. 相似文献
39.
Hisanao Takeuchi Motoshi Isobe Shoji Usui Keiichiro Muramatsu 《Bioscience, biotechnology, and biochemistry》2013,77(5):931-938
The effects of adrenalectomy on growth, some enzyme activities in the liver and kidney, and urinary excretion of urea, creatinine and creatine were investigated in rats fed the 10% casein diets containing 7% glycine with or without l-arginine and l-methionine (10C, 10C7G and 10C7ArgMet).Body weight gains of the intact 10C and 10C7GArgMet groups were almost same as the corresponding adrenalectomized groups. The body weight of the adrenalectomized 10C7G group was extremely decreased though that of the intact 10C7G group was maintained almost constant; but the decrease was recovered by the administration of hydrocortisone. The activities of liver arginase and carbamylphosphate synthetase were not affected by those diets. Liver serine dehydratase and ornithine δ-aminotransferase activities were increased in the intact 10C7G and 10C7GArgMet groups, but these increases were depressed by adrenalectomy. Glutamate-pyruvate transminase activities in the liver of intact 10C7G and 10C7GArgMet groups were also enhanced, but were extremely decreased in the corresponding adrenalectomized groups. Kidney transamidinase activity was not affected by adrenalectomy. The amount of urinary excreted urea was almost unchanged by adrenalectomy, but was increased by hydrocortisone administration. The amounts of excreted creatine of the adrenalectomized groups were generally larger than the corresponding intact groups, but slightly decreased by the administration of hydrocortisone. The amount of excreted creatinine was not generally affected by adrenalectomy. 相似文献
40.
Tsutomu Yamaguchi Noriyuki Muroya Masakazu Isobe Mamoru Sugiura 《Bioscience, biotechnology, and biochemistry》2013,77(5):999-1005
Out of some 750 strains of microorganisms, a potent bacterium for lipase production was isolated from soil and was identified as Chromobacterium viscosum.The bacterium accumulates lipase in culture fluid when grown aerobically at 26°C for 3 days in a medium composed of soluble starch, soy bean meal, lard and inorganic salts.Chromobacterium lipase had an optimum pH of 7.0 for activity at 37°C, and an optimal temperature of 65°C at pH 7.0. The enzyme retained 80% of the activity when heated for 10 min at 70°C. This lipase was capable of hydrolyzing a variety of natural fats and oils, and it was more active on lard and butter than on olive oil. The activity was stimulated by Ca2+, Mg2+, Mn2+ and inhibited by Cu2+, Hg2+ and Sn2+. It was not diminished but rather stimulated by a high concentration of bile-salts. 相似文献