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31.
Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility loci on chromosomes 1p, 14q, and 20p 总被引:2,自引:1,他引:1
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Arinami T Ohtsuki T Ishiguro H Ujike H Tanaka Y Morita Y Mineta M Takeichi M Yamada S Imamura A Ohara K Shibuya H Ohara K Suzuki Y Muratake T Kaneko N Someya T Inada T Yoshikawa T Toyota T Yamada K Kojima T Takahashi S Osamu O Shinkai T Nakamura M Fukuzako H Hashiguchi T Niwa SI Ueno T Tachikawa H Hori T Asada T Nanko S Kunugi H Hashimoto R Ozaki N Iwata N Harano M Arai H Ohnuma T Kusumi I Koyama T Yoneda H Fukumaki Y Shibata H Kaneko S Higuchi H Yasui-Furukori N Numachi Y Itokawa M 《American journal of human genetics》2005,77(6):937-944
The Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) is a multisite collaborative study group that was organized to create a national resource for affected sib pair (ASP) studies of schizophrenia in Japan. We used a high-density single-nucleotide–polymorphism (SNP) genotyping assay, the Illumina BeadArray linkage mapping panel (version 4) comprising 5,861 SNPs, to perform a genomewide linkage analysis of JSSLG samples comprising 236 Japanese families with 268 nonindependent ASPs with schizophrenia. All subjects were Japanese. Among these families, 122 families comprised the same subjects analyzed with short tandem repeat markers. All the probands and their siblings, with the exception of seven siblings with schizoaffective disorder, had schizophrenia. After excluding SNPs with high linkage disequilibrium, we found significant evidence of linkage of schizophrenia to chromosome 1p21.2-1p13.2 (LOD=3.39) and suggestive evidence of linkage to 14q11.2 (LOD=2.87), 14q11.2-q13.2 (LOD=2.33), and 20p12.1-p11.2 (LOD=2.33). Although linkage to these regions has received little attention, these regions are included in or partially overlap the 10 regions reported by Lewis et al. that passed the two aggregate criteria of a meta-analysis. Results of the present study—which, to our knowledge, is the first genomewide analysis of schizophrenia in ASPs of a single Asian ethnicity that is comparable to the analyses done of ASPs of European descent—indicate the existence of schizophrenia susceptibility loci that are common to different ethnic groups but that likely have different ethnicity-specific effects. 相似文献
32.
Superoxide production at phagosomal cup/phagosome through beta I protein kinase C during Fc gamma R-mediated phagocytosis in microglia 总被引:2,自引:0,他引:2
Ueyama T Lennartz MR Noda Y Kobayashi T Shirai Y Rikitake K Yamasaki T Hayashi S Sakai N Seguchi H Sawada M Sumimoto H Saito N 《Journal of immunology (Baltimore, Md. : 1950)》2004,173(7):4582-4589
Protein kinase C (PKC) plays a prominent role in immune signaling. To elucidate the signal transduction in a respiratory burst and isoform-specific function of PKC during FcgammaR-mediated phagocytosis, we used live, digital fluorescence imaging of mouse microglial cells expressing GFP-tagged molecules. betaI PKC, epsilonPKC, and diacylglycerol kinase (DGK) beta dynamically and transiently accumulated around IgG-opsonized beads (BIgG). Moreover, the accumulation of p47(phox), an essential cytosolic component of NADPH oxidase and a substrate for betaI PKC, at the phagosomal cup/phagosome was apparent during BIgG ingestion. Superoxide (O(2)(-)) production was profoundly inhibited by G?6976, a cPKC inhibitor, and dramatically increased by the DGK inhibitor, R59949. Ultrastructural analysis revealed that BIgG induced O(2)(-) production at the phagosome but not at the intracellular granules. We conclude that activation/accumulation of betaI PKC is involved in O(2)(-) production, and that O(2)(-) production is primarily initiated at the phagosomal cup/phagosome. This study also suggests that DGKbeta plays a prominent role in regulation of O(2)(-) production during FcgammaR-mediated phagocytosis. 相似文献
33.
Tomoko Furuya Kenzo Ikemoto Shigeto Kawauchi Atsunori Oga Shin'ichi Tsunoda Takashi Hirano Kohsuke Sasaki 《The journal of histochemistry and cytochemistry》2004,52(2):205-210
Immunohistochemical (IHC) examination is frequently necessary for a histological differential diagnosis of tumors. To simplify IHC examination, we have developed a novel device called a "multiplex-immunostain chip (MI chip)." The chip is a panel of antibodies contained in a silicon rubber plate that consists of 50 2-mm-diameter wells. A tissue section slide is placed on the plate and is fastened tightly with a specially designed clamp. The plate with the slide is then turned upside down, which applies the antibodies to the section. This technology allows IHC staining of a tissue section with 50 different antibodies in a single experiment, reducing the time, effort, and expense of IHC analysis. In addition, it enables pathologists to compare expression of multiple antigens on a tissue section simply by changing microscopic fields on a single slide. These features are unique to the MI chip technology. The method requires no expensive instruments. This device can be used in various applications in differential diagnosis of tumors and the field of cell biology. 相似文献
34.
35.
14-3-3eta is a novel regulator of parkin ubiquitin ligase 总被引:7,自引:0,他引:7
Mutation of the parkin gene, which encodes an E3 ubiquitin-protein ligase, is the major cause of autosomal recessive juvenile parkinsonism (ARJP). Although various substrates for parkin have been identified, the mechanisms that regulate the ubiquitin ligase activity of parkin are poorly understood. Here we report that 14-3-3eta, a chaperone-like protein present abundantly in neurons, could bind to parkin and negatively regulate its ubiquitin ligase activity. Furthermore, 14-3-3eta could bind to the linker region of parkin but not parkin with ARJP-causing R42P, K161N, and T240R mutations. Intriguingly, alpha-synuclein (alpha-SN), another familial Parkinson's disease (PD) gene product, abrogated the 14-3-3eta-induced suppression of parkin activity. alpha-SN could bind tightly to 14-3-3eta and consequently sequester it from the parkin-14-3-3eta complex. PD-causing A30P and A53T mutants of alpha-SN could not bind 14-3-3eta, and failed to activate parkin. Our findings indicate that 14-3-3eta is a regulator that functionally links parkin and alpha-SN. The alpha-SN-positive and 14-3-3eta-negative control of parkin activity sheds new light on the pathophysiological roles of parkin. 相似文献
36.
Barman HK Takami Y Ono T Nishijima H Sanematsu F Shibahara K Nakayama T 《Biochemical and biophysical research communications》2006,345(4):1547-1557
Histone acetyltransferase 1 (HAT1) is implicated for diacetylation of Lys-5 and Lys-12 of newly synthesized histone H4, the biological significance of which remains unclear. To investigate the in vivo role of HAT1, we generated HAT1-deficient DT40 clone (HAT1(-/-)). HAT1(-/-) cells exhibited greatly reduced diacetylation levels of Lys-5 and Lys-12, and acetylation level of Lys-5 of cytosolic and chromatin histones H4, respectively. The in vitro nucleosome assembly assay and in vivo MNase digestion assay revealed that HAT1 and diacetylation of Lys-5 and Lys-12 of histone H4 are dispensable for replication-coupled chromatin assembly. HAT1(-/-) cells had mild growth defect, conferring sensitivities to methyl methanesulfonate and camptothecin that enforce replication blocks creating DNA double strand breaks. Such heightened sensitivities were associated with prolonged late-S/G2 phase. These results indicate that HAT1 participates in recovering replication block-mediated DNA damages, probably through chromatin modulation based on acetylation of Lys-5 and Lys-12 of histone H4. 相似文献
37.
Shigemitsu T Ozaki S Saito Y Kuroda M Morita S Satoh S Masumura T 《Plant cell reports》2012,31(3):539-549
Rice seeds are potentially useful hosts for the production of pharmaceutical proteins. However, low yields of recombinant
proteins have been observed in many cases because recombinant proteins compete with endogenous storage proteins. Therefore,
we attempt to suppress endogenous seed storage proteins by RNA interference (RNAi) to develop rice seeds as a more efficient
protein expression system. In this study, human growth hormone (hGH) was expressed in transgenic rice seeds using an endosperm-specific
promoter from a 10 kDa rice prolamin gene. In addition, an RNAi cassette for reduction of endogenous storage protein expressions
was inserted into the hGH expression construct. Using this system, the expression levels of 13 kDa prolamin and glutelin were
effectively suppressed and hGH polypeptides accumulated to 470 μg/g dry weight at the maximum level in transgenic rice seeds.
These results suggest that the suppression of endogenous protein gene expression by RNAi could be of great utility for increasing
transgene products. 相似文献
38.
Munehiro Uda Hiroaki Kawasaki Ayako Shigenaga Takeshi Baba Fumiyuki Yamakura 《Bioscience reports》2012,32(6):521-530
Nitration of tryptophan residues is a novel post-translational modification. In the present
study, we examined whether NO2Trp (nitrotryptophan)-containing proteins are produced in
the hippocampus and cerebellum of the adult rat under physiological conditions in
vivo. Using Western blot analysis with anti-6-NO2Trp-specific antibody, we found
many similar immunoreactive spots in the protein extracts from both regions. These spots were
subsequently subjected to trypsin digestion and LC-ESI-MS/MS (LC-electrospray ionization-tandem MS)
analysis. We identified several cytoskeletal proteins and glycolytic enzymes as
NO2Trp-containing proteins and determined the position of nitrated tryptophan residues
with significant ion score levels (P<0.05) in several proteins in both
regions. We also observed that the total amount of NO2Trp-containing proteins in the
cerebellum was significantly greater than that in the hippocampus (P<0.05).
Moreover, IP (immunoprecipitation) assays using anti-aldolase C antibody showed that the relative
intensity of immunostaining for NO2Trp over aldolase C was much higher in cerebellum than
in hippocampus. The amounts of nNOS (neuronal nitric oxide synthase) and eNOS (endothelial nitric
oxide synthase) were much greater in cerebellum than in hippocampus. This is the first evidence of
several specific sites of nitrated tryptophan in proteins under physiological conditions in
vivo. 相似文献
39.
Nishizawa T Tago K Oshima K Hattori M Ishii S Otsuka S Senoo K 《Journal of bacteriology》2012,194(5):1255
We report the finished and annotated genome sequence of a denitrifying and N(2)O-reducing betaproteobacterium, Azoarcus sp. strain KH32C. The genome is composed of one chromosome and one megaplasmid and contains genes for plant-microbe interactions and the gene clusters for aromatic-compound degradations. 相似文献
40.
Watanabe Y Kitazawa S Fujii H Nemoto T Hirayama S Nagase H 《Bioorganic & medicinal chemistry letters》2012,22(8):2689-2692
A novel opioid ligand possessing a stable and cyclic imine 16 and its derivatives with an azabicyclo[2.2.2]octane skeleton were synthesized. The imine 16 showed higher affinity for the μ receptor than compound 21 with an oxabicyclo[2.2.2]octane skeleton. Azabicyclo[2.2.2]octane derivative 18d with a cyclopropylmethyl group on the 8-nitrogen showed the highest affinity for the μ receptor among the synthesized derivatives. 相似文献