全文获取类型
收费全文 | 1888篇 |
免费 | 86篇 |
国内免费 | 1篇 |
出版年
2023年 | 2篇 |
2022年 | 9篇 |
2021年 | 31篇 |
2020年 | 14篇 |
2019年 | 24篇 |
2018年 | 45篇 |
2017年 | 29篇 |
2016年 | 42篇 |
2015年 | 66篇 |
2014年 | 92篇 |
2013年 | 133篇 |
2012年 | 167篇 |
2011年 | 149篇 |
2010年 | 104篇 |
2009年 | 75篇 |
2008年 | 143篇 |
2007年 | 146篇 |
2006年 | 131篇 |
2005年 | 93篇 |
2004年 | 127篇 |
2003年 | 90篇 |
2002年 | 93篇 |
2001年 | 12篇 |
2000年 | 9篇 |
1999年 | 23篇 |
1998年 | 15篇 |
1997年 | 11篇 |
1996年 | 6篇 |
1995年 | 9篇 |
1994年 | 8篇 |
1993年 | 5篇 |
1992年 | 15篇 |
1991年 | 3篇 |
1990年 | 8篇 |
1989年 | 2篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 4篇 |
1984年 | 8篇 |
1983年 | 3篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 4篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1970年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有1975条查询结果,搜索用时 687 毫秒
31.
Tomohiro Nishimura Shinya Sato Wittaya Tawong Hiroshi Sakanari Keita Uehara Md Mahfuzur Rahman Shah Shoichiro Suda Takeshi Yasumoto Yohsuke Taira Haruo Yamaguchi Masao Adachi 《PloS one》2013,8(4)
Background
The marine epiphytic dinoflagellate genus Gambierdiscus produce toxins that cause ciguatera fish poisoning (CFP): one of the most significant seafood-borne illnesses associated with fish consumption worldwide. So far, occurrences of CFP incidents in Japan have been mainly reported in subtropical areas. A previous phylogeographic study of Japanese Gambierdiscus revealed the existence of two distinct phylotypes: Gambierdiscus sp. type 1 from subtropical and Gambierdiscus sp. type 2 from temperate areas. However, details of the genetic diversity and distribution for Japanese Gambierdiscus are still unclear, because a comprehensive investigation has not been conducted yet.Methods/Principal Finding
A total of 248 strains were examined from samples mainly collected from western and southern coastal areas of Japan during 2006–2011. The SSU rDNA, the LSU rDNA D8–D10 and the ITS region were selected as genetic markers and phylogenetic analyses were conducted. The genetic diversity of Japanese Gambierdiscus was high since five species/phylotypes were detected: including two reported phylotypes (Gambierdiscus sp. type 1 and Gambierdiscus sp. type 2), two species of Gambierdiscus (G. australes and G. cf. yasumotoi) and a hitherto unreported phylotype Gambierdiscus sp. type 3. The distributions of type 3 and G. cf. yasumotoi were restricted to the temperate and the subtropical area, respectively. On the other hand, type 1, type 2 and G. australes occurred from the subtropical to the temperate area, with a tendency that type 1 and G. australes were dominant in the subtropical area, whereas type 2 was dominant in the temperate area. By using mouse bioassay, type 1, type 3 and G. australes exhibited mouse toxicities.Conclusions/Significance
This study revealed a surprising diversity of Japanese Gambierdiscus and the distribution of five species/phylotypes displayed clear geographical patterns in Japanese coastal areas. The SSU rDNA and the LSU rDNA D8–D10 as genetic markers are recommended for further use. 相似文献32.
Robert K. Naviaux Zarazuela Zolkipli Lin Wang Tomohiro Nakayama Jane C. Naviaux Thuy P. Le Michael A. Schuchbauer Mihael Rogac Qingbo Tang Laura L. Dugan Susan B. Powell 《PloS one》2013,8(3)
Background
Autism spectrum disorders (ASDs) are caused by both genetic and environmental factors. Mitochondria act to connect genes and environment by regulating gene-encoded metabolic networks according to changes in the chemistry of the cell and its environment. Mitochondrial ATP and other metabolites are mitokines—signaling molecules made in mitochondria—that undergo regulated release from cells to communicate cellular health and danger to neighboring cells via purinergic signaling. The role of purinergic signaling has not yet been explored in autism spectrum disorders.Objectives and Methods
We used the maternal immune activation (MIA) mouse model of gestational poly(IC) exposure and treatment with the non-selective purinergic antagonist suramin to test the role of purinergic signaling in C57BL/6J mice.Results
We found that antipurinergic therapy (APT) corrected 16 multisystem abnormalities that defined the ASD-like phenotype in this model. These included correction of the core social deficits and sensorimotor coordination abnormalities, prevention of cerebellar Purkinje cell loss, correction of the ultrastructural synaptic dysmorphology, and correction of the hypothermia, metabolic, mitochondrial, P2Y2 and P2X7 purinergic receptor expression, and ERK1/2 and CAMKII signal transduction abnormalities.Conclusions
Hyperpurinergia is a fundamental and treatable feature of the multisystem abnormalities in the poly(IC) mouse model of autism spectrum disorders. Antipurinergic therapy provides a new tool for refining current concepts of pathogenesis in autism and related spectrum disorders, and represents a fresh path forward for new drug development. 相似文献33.
Introduction
Patients with schizophrenia elicit cognitive decline from the early phase of the illness. Mismatch negativity (MMN) has been shown to be associated with cognitive function. We investigated the current source density of duration mismatch negativity (dMMN), by using low-resolution brain electromagnetic tomography (LORETA), and neuropsychological performance in subjects with early schizophrenia.Methods
Data were obtained from 20 patients meeting DSM-IV criteria for schizophrenia or schizophreniform disorder, and 20 healthy control (HC) subjects. An auditory odd-ball paradigm was used to measure dMMN. Neuropsychological performance was evaluated by the brief assessment of cognition in schizophrenia Japanese version (BACS-J).Results
Patients showed smaller dMMN amplitudes than those in the HC subjects. LORETA current density for dMMN was significantly lower in patients compared to HC subjects, especially in the temporal lobes. dMMN current density in the frontal lobe was positively correlated with working memory performance in patients.Conclusions
This is the first study to identify brain regions showing smaller dMMN current density in early schizophrenia. Further, poor working memory was associated with decreased dMMN current density in patients. These results are likely to help understand the neural basis for cognitive impairment of schizophrenia. 相似文献34.
35.
36.
Yoshiteru Sasaki Soichi Sano Masaki Nakahara Shigeo Murata Kohei Kometani Yuichi Aiba Shinji Sakamoto Yoshihiro Watanabe Keiji Tanaka Tomohiro Kurosaki Kazuhiro Iwai 《The EMBO journal》2013,32(18):2463-2476
The linear ubiquitin chain assembly complex (LUBAC) plays a crucial role in activating the canonical NF‐κB pathway, which is important for B‐cell development and function. Here, we describe a mouse model (B‐HOIPΔlinear) in which the linear polyubiquitination activity of LUBAC is specifically ablated in B cells. Canonical NF‐κB and ERK activation, mediated by the tumour necrosis factor (TNF) receptor superfamily receptors CD40 and TACI, was impaired in B cells from B‐HOIPΔlinear mice due to defective activation of the IKK complex; however, B‐cell receptor (BCR)‐mediated activation of the NF‐κB and ERK pathways was unaffected. B‐HOIPΔlinear mice show impaired B1‐cell development and defective antibody responses to thymus‐dependent and thymus‐independent II antigens. Taken together, these data suggest that LUBAC‐mediated linear polyubiquitination is essential for B‐cell development and activation, possibly via canonical NF‐κB and ERK activation induced by the TNF receptor superfamily, but not by the BCR. 相似文献
37.
Tomohiro Watanabe Hisaya Kojima Yoshinori Takano Manabu Fukui 《Systematic and applied microbiology》2013
The diversity of sulfate-reducing prokaryotes (SRPs) and sulfur-oxidizing prokaryotes (SOPs) in freshwater lake ecosystems was investigated by cloning and sequencing of the aprA gene, which encodes for a key enzyme in dissimilatory sulfate reduction and sulfur oxidation. To understand their diversity better, the spatial distribution of aprA genes was investigated in sediments collected from six geographically distant lakes in Antarctica and Japan, including a hypersaline lake for comparison. The microbial community compositions of freshwater sediments and a hypersaline sediment showed notable differences. The clones affiliated with Desulfobacteraceae and Desulfobulbaceae were frequently detected in all freshwater lake sediments. The SOP community was mainly composed of four major phylogenetic groups. One of them formed a monophyletic cluster with a sulfur-oxidizing betaproteobacterium, Sulfuricella denitrificans, but the others were not assigned to specific genera. In addition, the AprA sequences, which were not clearly affiliated to either SRP or SOP lineages, dominated the libraries from four freshwater lake sediments. The results showed the wide distribution of some sulfur-cycle prokaryotes across geographical distances and supported the idea that metabolic flexibility is an important feature for SRP survival in low-sulfate environments. 相似文献
38.
Wei Zou Monica Croke Tomohiro Fukunaga Thomas J. Broekelmann Robert P. Mecham Steven L. Teitelbaum 《Journal of cellular biochemistry》2013,114(8):1871-1878
The αvβ3 integrin stimulates the resorptive capacity of the differentiated osteoclast (OC) by organizing its cytoskeleton via the tyrosine kinase, Syk. Thus, Syk‐deficient OCs fails to spread or form actin rings, in vitro and in vivo. The Syk family of tyrosine kinases consists of Syk itself and Zap70 which are expressed by different cell types. Because of their structural similarity, and its compensatory properties in other cells, we asked if Zap70 can substitute for absence of Syk in OCs. While expression of Syk, as expected, normalizes the cytoskeletal abnormalities of Syk?/? OCs, Zap70 fails do so. In keeping with this observation, Syk, but not Zap70, rescues αvβ3 integrin‐induced SLP76 phosphorylation in Syk?/? OCs. Furthermore the kinase sequence of Syk partially rescues the Syk?/? phenotype but full normalization also requires its SH2 domains. Surprisingly, expression of Zap70 inhibits WT OC spreading, actin ring formation and bone resorptive activity, but not differentiation. In keeping with arrested cytoskeletal organization, Zap70 blocks integrin‐activated endogenous Syk and Vav3, SLP76 phosphorylation. Such inhibition requires Zap70 kinase activity, as it is abolished by mutation of the Zap70 kinase domain. Thus, while the kinase domain of Syk is uniquely required for OC function that of Zap70 inhibits it. J. Cell. Biochem. 114: 1871–1878, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
39.
40.
Makoto Hibi Takashi Kawashima Pavel M. Sokolov Sergey V. Smirnov Tomohiro Kodera Masakazu Sugiyama Sakayu Shimizu Kenzo Yokozeki Jun Ogawa 《Applied microbiology and biotechnology》2013,97(6):2467-2472
l-Leucine 5-hydroxylase (LdoA) previously found in Nostoc punctiforme PCC 73102 is a novel type of Fe(II)/α-ketoglutarate-dependent dioxygenase. LdoA catalyzed regio- and stereoselective hydroxylation of l-leucine and l-norleucine into (2S,4S)-5-hydroxyleucine and (2S)-5-hydroxynorleucine, respectively. Moreover, LdoA catalyzed sulfoxidation of l-methionine and l-ethionine in the same manner as previously described l-isoleucine 4-hydroxylase. Therefore LdoA should be a promising biocatalyst for effective production of industrially useful amino acids. 相似文献