全文获取类型
收费全文 | 1185篇 |
免费 | 50篇 |
出版年
2022年 | 4篇 |
2021年 | 20篇 |
2020年 | 5篇 |
2019年 | 7篇 |
2018年 | 5篇 |
2017年 | 14篇 |
2016年 | 30篇 |
2015年 | 35篇 |
2014年 | 47篇 |
2013年 | 89篇 |
2012年 | 68篇 |
2011年 | 65篇 |
2010年 | 49篇 |
2009年 | 44篇 |
2008年 | 78篇 |
2007年 | 66篇 |
2006年 | 77篇 |
2005年 | 76篇 |
2004年 | 74篇 |
2003年 | 94篇 |
2002年 | 68篇 |
2001年 | 21篇 |
2000年 | 11篇 |
1999年 | 9篇 |
1998年 | 14篇 |
1997年 | 15篇 |
1996年 | 6篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 11篇 |
1992年 | 11篇 |
1991年 | 4篇 |
1990年 | 8篇 |
1989年 | 6篇 |
1988年 | 5篇 |
1987年 | 9篇 |
1986年 | 5篇 |
1985年 | 8篇 |
1984年 | 17篇 |
1983年 | 7篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1980年 | 7篇 |
1979年 | 6篇 |
1978年 | 2篇 |
1976年 | 5篇 |
1973年 | 5篇 |
1971年 | 3篇 |
1967年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有1235条查询结果,搜索用时 343 毫秒
101.
Roles of prostaglandin synthesis in excitotoxic brain diseases 总被引:2,自引:0,他引:2
Cyclooxygenase (COX) is a rate-limiting enzyme in prostaglandin synthesis. COX consists of two isoforms, constitutive COX-1 and inducible COX-2. We have first found that COX-2 expression in the brain is tightly regulated by neuronal activity under physiological conditions, and electroconvulsive seizure robustly induces COX-2 mRNA in the brain. Our recent in-depth studies reveal COX-2 expression is divided into two phases, early in neurons and late in non-neuronal cells, such as endothelial cells or astrocytes. In this review, we present that early synthesized COX-2 facilitates the recurrence of hippocampal seizures in rapid kindling model, and late induced COX-2 stimulates hippocampal neuron loss after kainic acid treatment. Hence, we consider the potential role of COX-2 inhibitors as a new therapeutic drug for a neuronal loss after seizure or focal cerebral ischemia. The short-term and sub-acute medication of selective COX-2 inhibitors that suppresses an elevation of prostaglandin E(2) (PGE(2)) may be an effective treatment to prevent neuronal loss after onset of neuronal excitatory diseases. This review also discusses a novel role of vascular endothelial cells in brain diseases. We found that these cells produce PGE(2) by synthesizing COX-2 and microsomal prostaglandin E synthase-1 (mPGES-1) in response to excitotoxicity and neuroinflammation. We also show a possible mechanisms of neuronal damage associated with seizure via astrocytes and endothelial cells. Further analysis of the interaction among neurons, astrocytes and endothelial cells may provide a better understanding of the processes of neuropathological disorders, as well as facilitating the development of new treatments. 相似文献
102.
Miura K Yoshiura K Miura S Shimada T Yamasaki K Yoshida A Nakayama D Shibata Y Niikawa N Masuzaki H 《Human genetics》2007,121(5):631-633
Here we provided the first genetic evidence for an association between the degree of apocrine colostrum secretion and human
earwax type. Genotyping at the earwax-type locus, rs17822931 within the ABCC11 gene, revealed that 155 of 225 Japanese women were dry-type and 70 wet-type. Frequency of women without colostrum among dry-type
women was significantly higher than that among wet-type women (P < 0.0002), and the measurable colostrum volume in dry-type women was significantly smaller than in wet-type women (P = 0.0341). 相似文献
103.
Endogenous cannabinoids (endocannabinoids) serve as retrograde messengers at synapses in various regions of the brain. They are released from postsynaptic neurons and cause transient and long-lasting reduction of neurotransmitter release through activation of presynaptic cannabinoid receptors. Endocannabinoid release is induced either by increased postsynaptic Ca(2+) levels or by activation of G(q/11)-coupled receptors. When these two stimuli coincide, endocannabinoid release is markedly enhanced, which is attributed to the Ca(2+) dependency of phospholipase Cbeta (PLCbeta). This Ca(2+)-assisted receptor-driven endocannabinoid release is suggested to participate in various forms of synaptic plasticity, including short-term associative plasticity in the cerebellum and spike-timing-dependent long-term depression in the somatosensory cortex. In these forms of plasticity, PLCbeta seems to function as a coincident detector of presynaptic and postsynaptic activities. 相似文献
104.
Hirano K Nakajima M Asano K Nishiyama T Sakakibara H Kojima M Katoh E Xiang H Tanahashi T Hasebe M Banks JA Ashikari M Kitano H Ueguchi-Tanaka M Matsuoka M 《The Plant cell》2007,19(10):3058-3079
In rice (Oryza sativa) and Arabidopsis thaliana, gibberellin (GA) signaling is mediated by GIBBERELLIN-INSENSITIVE DWARF1 (GID1) and DELLA proteins in collaboration with a GA-specific F-box protein. To explore when plants evolved the ability to perceive GA by the GID1/DELLA pathway, we examined these GA signaling components in the lycophyte Selaginella moellendorffii and the bryophyte Physcomitrella patens. An in silico search identified several homologs of GID1, DELLA, and GID2, a GA-specific F-box protein in rice, in both species. Sm GID1a and Sm GID1b, GID1 proteins from S. moellendorffii, showed GA binding activity in vitro and interacted with DELLA proteins from S. moellendorffii in a GA-dependent manner in yeast. Introduction of constitutively expressed Sm GID1a, Sm G1D1b, and Sm GID2a transgenes rescued the dwarf phenotype of rice gid1 and gid2 mutants. Furthermore, treatment with GA(4), a major GA in S. moellendorffii, caused downregulation of Sm GID1b, Sm GA20 oxidase, and Sm GA3 oxidase and degradation of the Sm DELLA1 protein. These results demonstrate that the homologs of GID1, DELLA, and GID2 work in a similar manner in S. moellendorffii and in flowering plants. Biochemical studies revealed that Sm GID1s have different GA binding properties from GID1s in flowering plants. No evidence was found for the functional conservation of these genes in P. patens, indicating that GID1/DELLA-mediated GA signaling, if present, differs from that in vascular plants. Our results suggest that GID1/DELLA-mediated GA signaling appeared after the divergence of vascular plants from the moss lineage. 相似文献
105.
Sasaki H Nonaka J Sasaki T Nakai Y 《Journal of industrial microbiology & biotechnology》2007,34(2):105-110
We isolated ammonia-assimilating microorganisms from the livestock manure treatment systems and evaluated their ammonia-assimilating
ability. Many isolates utilized ammonia at high rates when they were purely cultivated in a nitrogen-limited medium to which
sterilized lagoon extract had been added. Some isolates that were immobilized in polyvinyl alcohol (PVA) utilized ammonia
present in the media containing viable lagoon microorganisms. Staining with 4′,6′-diamidino-2-phenylindole (DAPI) indicated
that the immobilized high ammonia-assimilating isolates grew dominantly within the PVA beads. High ammonia-assimilating isolates
in the mixed culture containing viable lagoon microorganisms were identified as Pseudomonas spp. and member of Rhizobiaceae species by partial sequencing of the 16S ribosomal DNA. 相似文献
106.
Molecular survey of Babesia microti, Ehrlichia species and Candidatus neoehrlichia mikurensis in wild rodents from Shimane Prefecture, Japan 总被引:1,自引:0,他引:1
Tabara K Arai S Kawabuchi T Itagaki A Ishihara C Satoh H Okabe N Tsuji M 《Microbiology and immunology》2007,51(4):359-367
A significant number of patients are diagnosed with "fevers of unknown origin" (FUO) in Shimane Prefecture in Japan where tick-borne diseases are endemic. We conducted molecular surveys for Babesia microti, Ehrlichia species, and Candidatus Neoehrlichia mikurensis in 62 FUO cases and 62 wild rodents from Shimane Prefecture, Japan. PCR using primers specific for the Babesia 18S small-subunit rRNA (rDNA) gene and Anaplasmataceae groESL amplified products from 45% (28/62) and 25.8% (16/62) of captured mice, respectively. Of the 28 18S rDNA PCR positives, 23 and five samples were positive for Hobetsu- and Kobe-type B. microti, respectively. In contrast, of the 16 groESL PCR positives, eight, one and seven samples were positive for Ehrlichia muris, Ehrlichia sp. HF565 and Candidatus N. mikurensis, respectively. Inoculation of selected blood samples into Golden Syrian hamsters indicated the presence of Hobetsu- and Kobe-type B. microti in four and one sample, respectively. Isolation of the latter strain was considered important as previous studies suggested that the distribution of this type was so far confined to Awaji Island in Hyogo Prefecture, where the first case of transfusion-associated human babesiosis originated. DNA samples from 62 FUO human cases tested negative for B. microti 18S rDNA gene, Anaplasmataceae groESL gene, Rickettsia japonica 17K genus-common antigen gene and Orientia tsutsugamushi 56K antigen gene by PCRs. We also conducted seroepidemiological surveys on 62 human sera collected in Shimane Prefecture from the FUO patients who were suspected of carrying tick-borne diseases. However, indirect immunofluorescent antibody tests using B. microti- and E. muris-infected cells detected IgG against E. muris in only a single positive sample. This study demonstrates the presence of several potentially important tick-borne pathogens in Shimane Prefecture and suggests the need for further study on the causative agents of FUOs. 相似文献
107.
Furukawa K Yoshimi A Furukawa T Hoshi Y Hagiwara D Sato N Fujioka T Mizutani O Mizuno T Kobayashi T Abe K 《Bioscience, biotechnology, and biochemistry》2007,71(7):1724-1730
The Aspergillus nidulans high-osmolarity glycerol response (AnHOG) pathway is involved in osmoadaptation. We found that fludioxonil, a fungicide, causes improper activation of HogA mitogen-activated protein kinase (MAPK) in A. nidulans. Here we present novel reporter systems for monitoring activation of the AnHOG pathway. The promoter region of gfdB (glycerol-3-phosphate dehydrogenase), whose expression depends on the presence of HogA, was fused to a beta-glucuronidase uidA gene (GUS) to construct the reporter, which was introduced into A. nidulans wild type and hogADelta. Increased GUS activity was detected in the wild type only when it was treated with high osmolarity or fludioxonil, while reporter activity was scarcely stimulated in the hogADelta mutant. These results indicate that the reporter activity is controlled via HogA activation. Furthermore, we present possible applications of the reporter systems in screening new antifungal compounds. 相似文献
108.
109.
Masaaki Okamoto Susumu Imai Mayu Miyanohara Wataru Saito Yasuko Momoi Yoshiaki Nomura Tomoko Ikawa Takumi Ogawa Takako Miyabe‐Nishiwaki Akihisa Kaneko Akino Watanabe Shohei Watanabe Misato Hayashi Masaki Tomonaga Nobuhiro Hanada 《Microbiology and immunology》2015,59(9):526-532
Three strains TKU9, TKU49 and TKU50T, were isolated from the oral cavities of chimpanzees (Pan troglodytes). The isolates were all gram‐positive, facultative anaerobic cocci that lacked catalase activity. Analysis of partial 16S rRNA gene sequences showed that the most closely related species was Streptococcus infantis (96.7%). The next most closely related species to the isolates were S. rubneri, S. mitis, S. peroris and S. australis (96.6 to 96.4%). Based on the rpoB and gyrB gene sequences, TKU50T was clustered with other member of the mitis group. Enzyme activity and sugar fermentation patterns differentiated this novel bacterium from other members of the mitis group streptococci. The DNA G + C content of strain TKU50T was 46.7 mol%, which is the highest reported value for members of the mitis group (40–46 mol%). On the basis of the phenotypic characterization, partial 16S rRNA gene and sequences data for two housekeeping gene (gyrB and rpoB), we propose a novel taxa, S. panodentis for TKU 50T (type strain = CM 30579T = DSM 29921T), for these newly described isolates. 相似文献
110.
Takako Usuki Hiromichi Sakai Takao Shionoya Naruki Sato Fumio Sakane 《The journal of histochemistry and cytochemistry》2015,63(1):57-68
The functions of type II diacylglycerol kinase (DGK) δ and -η in the brain are still unclear. As a first step, we investigated the spatial and temporal expression of DGKδ and -η in the brains of mice. DGKδ2, but not DGKδ1, was highly expressed in layers II–VI of the cerebral cortex; CA–CA3 regions and dentate gyrus of hippocampus; mitral cell, glomerular and granule cell layers of the olfactory bulb; and the granule cell layer in the cerebellum in 1- to 32-week-old mice. DGKδ2 was expressed just after birth, and its expression levels dramatically increased from weeks 1 to 4. A substantial amount of DGKη (η1/η2) was detected in layers II–VI of the cerebral cortex, CA1 and CA2 regions and dentate gyrus of the hippocampus, mitral cell and glomerular layers of the olfactory bulb, and Purkinje cells in the cerebellum of 1- to 32-week-old mice. DGKη2 expression reached maximum levels at P5 and decreased by 4 weeks, whereas DGKη1 increased over the same time frame. These results indicate that the expression patterns of DGK isozymes differ from each other and also from other isozymes, and this suggests that DGKδ and -η play distinct and specific roles in the brain. 相似文献