全文获取类型
收费全文 | 1922篇 |
免费 | 158篇 |
专业分类
2080篇 |
出版年
2023年 | 8篇 |
2022年 | 17篇 |
2021年 | 34篇 |
2020年 | 18篇 |
2019年 | 17篇 |
2018年 | 34篇 |
2017年 | 38篇 |
2016年 | 47篇 |
2015年 | 89篇 |
2014年 | 105篇 |
2013年 | 118篇 |
2012年 | 133篇 |
2011年 | 132篇 |
2010年 | 74篇 |
2009年 | 51篇 |
2008年 | 107篇 |
2007年 | 101篇 |
2006年 | 66篇 |
2005年 | 74篇 |
2004年 | 93篇 |
2003年 | 84篇 |
2002年 | 91篇 |
2001年 | 40篇 |
2000年 | 41篇 |
1999年 | 40篇 |
1998年 | 30篇 |
1997年 | 27篇 |
1996年 | 25篇 |
1995年 | 21篇 |
1994年 | 18篇 |
1993年 | 19篇 |
1992年 | 31篇 |
1991年 | 21篇 |
1990年 | 18篇 |
1989年 | 20篇 |
1988年 | 29篇 |
1987年 | 20篇 |
1985年 | 11篇 |
1984年 | 15篇 |
1983年 | 6篇 |
1982年 | 12篇 |
1981年 | 8篇 |
1980年 | 7篇 |
1979年 | 9篇 |
1978年 | 11篇 |
1977年 | 9篇 |
1976年 | 7篇 |
1975年 | 8篇 |
1967年 | 10篇 |
1966年 | 8篇 |
排序方式: 共有2080条查询结果,搜索用时 0 毫秒
61.
Yuka Tanaka Tomoko Inoue-Yokoo Kasem Kulkeaw Chiyo Yanagi-Mizuochi Senji Shirasawa Yoichi Nakanishi Daisuke Sugiyama 《PloS one》2015,10(9)
In mice, hematopoietic cells home to bone marrow from fetal liver prenatally. To elucidate mechanisms underlying homing, we performed immunohistochemistry with the hematopoietic cell marker c-Kit, and observed c-Kit(+) cells localized inside muscle surrounding bone after 14.5 days post coitum. Flow cytometric analysis showed that CD45(+) c-Kit(+) hematopoietic cells were more abundant in muscle than in bone marrow between 14.5 and 17.5 days post coitum, peaking at 16.5 days post coitum. CD45(+) c-Kit(+) cells in muscle at 16.5 days post coitum exhibited higher expression of Gata2, among several hematopoietic genes, than did fetal liver or bone marrow cells. Colony formation assays revealed that muscle hematopoietic cells possess hematopoietic progenitor activity. Furthermore, exo utero transplantation revealed that fetal liver hematopoietic progenitor cells home to muscle and then to BM. Our findings demonstrate that hematopoietic progenitor cell homing occurs earlier than previously reported and that hematopoietic progenitor cells reside in muscle tissue before bone marrow hematopoiesis occurs during mouse embryogenesis. 相似文献
62.
A comparison of allozyme variation, restriction fragment length polymorphisms in the mitochondrial DNA and partial sequences of the ND II gene (496 bp) was made among two lacustrine populations of the piscivorous chub (Opsariichthys uncirostris uncirostris) in Japan, four fluvial populations in Korea, one lacustrine population in Russia and one specimen from the Amur River (O. u. amurensis). All analyses indicate that the Japanese populations of piscivorous chub are separable from the Asian mainland populations of Korea and Russia. The latter populations were further divided into the Korean and Russian fish. Although opinions are divided on the phylogenetic position of the population in Lake Mikata, Japan, which shows unique morphological traits intermediate between those of the population in Lake Biwa and the mainland populations, the current analysis indicates a closer relationship to the population in Lake Biwa. 相似文献
63.
Takashi Kajitani Mimi Tamamori-Adachi Hiroko Okinaga Minoru Chikamori Masayoshi Iizuka Tomoki Okazaki 《Biochemical and biophysical research communications》2011,(3):375
Elevated parathyroid hormone-related protein (PTHrP) is responsible for humoral hypercalcemia of malignancy (HHM), which is of clinical significance in treatment of terminal patients with malignancies. Steroid hormones were known to cause suppression of PTHrP expression. However, detailed studies linking multiple steroid hormones to PTHrP expression are lacking. Here we studied PTHrP expression in response to steroid hormones in four cell lines with excessive PTHrP production. Our study established that steroid hormones negatively regulate PTHrP expression. Vitamin D receptor, estrogen receptor α, glucocorticoid receptor, and progesterone receptor, were required for repression of PTHrP expression by the cognate ligands. A notable exception was the androgen receptor, which was dispensable for suppression of PTHrP expression in androgen-treated cells. We propose a pathway(s) involving nuclear receptors to suppress PTHrP expression. 相似文献
64.
65.
Ohi K Hashimoto R Yasuda Y Nemoto K Ohnishi T Fukumoto M Yamamori H Umeda-Yano S Okada T Iwase M Kazui H Takeda M 《PloS one》2012,7(1):e29780
Background
The rs12807809 single-nucleotide polymorphism in NRGN is a genetic risk variant with genome-wide significance for schizophrenia. The frequency of the T allele of rs12807809 is higher in individuals with schizophrenia than in those without the disorder. Reduced immunoreactivity of NRGN, which is expressed exclusively in the brain, has been observed in Brodmann areas (BA) 9 and 32 of the prefrontal cortex in postmortem brains from patients with schizophrenia compared with those in controls.Methods
Genotype effects of rs12807809 were investigated on gray matter (GM) and white matter (WM) volumes using magnetic resonance imaging (MRI) with a voxel-based morphometry (VBM) technique in a sample of 99 Japanese patients with schizophrenia and 263 healthy controls.Results
Although significant genotype-diagnosis interaction either on GM or WM volume was not observed, there was a trend of genotype-diagnosis interaction on GM volume in the left anterior cingulate cortex (ACC). Thus, the effects of NRGN genotype on GM volume of patients with schizophrenia and healthy controls were separately investigated. In patients with schizophrenia, carriers of the risk T allele had a smaller GM volume in the left ACC (BA32) than did carriers of the non-risk C allele. Significant genotype effect on other regions of the GM or WM was not observed for either the patients or controls.Conclusions
Our findings suggest that the genome-wide associated genetic risk variant in the NRGN gene may be related to a small GM volume in the ACC in the left hemisphere in patients with schizophrenia. 相似文献66.
Morita H Zaima K Koga I Saito A Tamamoto H Okazaki H Kaneda T Hashimoto T Asakawa Y 《Bioorganic & medicinal chemistry》2011,19(13):4051-4056
Vasorelaxant effects of a series of bis(bibenzyls) from liverworts such as Marchantia polymorpha and Marchantia paleacea on rat aorta demonstrated that they relaxed phenylephrine (PE)-induced contractions, which may be mediated through the increased release of NO from endothelial cells as well as opening of K(+) channels, and inhibition of Ca(2+) influx through voltage-dependent Ca(2+) channels (VDCs) and/or receptor-operated Ca(2+) channels (ROCs). Structure-activity relationship based on their structures was discussed. The presence of two aromatic rings which can be connected through two atoms bridge spacer may play an important role for vasorelaxant effect. 相似文献
67.
Pierson T Matrakas D Taylor YU Manyam G Morozov VN Zhou W van Hoek ML 《Journal of proteome research》2011,10(3):954-967
We have isolated and characterized outer membrane vesicles (OMVs) from Francisella. Transport of effector molecules through secretion systems is a major mechanism by which Francisella tularensis alters the extracellular proteome and interacts with the host during infection. Outer membrane vesicles produced by Francisella were examined using TEM and AFM and found to be 43-125 nm in size, representing another potential mechanism for altering the extracellular environment. A proteomic analysis (LC-MS/MS) of OMVs from F. novicida and F. philomiragia identified 416 (F. novicida) and 238 (F. philomiragia) different proteins, demonstrating that OMVs are an important contributor to the extracellular proteome. Many of the identified OMV proteins have a demonstrated role in Francisella pathogenesis. Biochemical assays demonstrated that Francisella OMVs possess acid phosphatase and hemolytic activities that may affect host cells during infection, and are cytotoxic toward murine macrophages in cell culture. OMVs have been previously used as a human vaccine against Neisseria meningitidis . We hypothesized that Francisella OMVs could be useful as a novel Francisella vaccine. Vaccinated BALB/C mice challenged with up to 50 LD50 of Francisella showed statistically significant protection when compared to control mice. In the context of these new findings, we discuss the relevance of OMVs in Francisella pathogenesis as well as their potential use as a vaccine. 相似文献
68.
Gelman AE Okazaki M Lai J Kornfeld CG Kreisel FH Richardson SB Sugimoto S Tietjens JR Patterson GA Krupnick AS Kreisel D 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(7):4754-4762
Acute rejection continues to present a major obstacle to successful lung transplantation. Although CD4(+) T lymphocytes are critical for the rejection of some solid organ grafts, the role of CD4(+) T cells in the rejection of lung allografts is largely unknown. In this study, we demonstrate in a novel model of orthotopic vascularized mouse lung transplantation that acute rejection of lung allografts is independent of CD4(+) T cell-mediated allorecognition pathways. CD4(+) T cell-independent rejection occurs in the absence of donor-derived graft-resident hematopoietic APCs. Furthermore, blockade of the CD28/B7 costimulatory pathways attenuates acute lung allograft rejection in the absence of CD4(+) T cells, but does not delay acute rejection when CD4(+) T cells are present. Our results provide new mechanistic insight into the acute rejection of lung allografts and highlight the importance of identifying differences in pathways that regulate the rejection of various organs. 相似文献
69.
Involvement of herpes simplex virus type 1 UL13 protein kinase in induction of SOCS genes,the negative regulators of cytokine signaling 下载免费PDF全文
70.
Osamu Ichikawa Kazuhiko Okazaki Hiroyuki Nakahira Megumi Maruyama Ryu Nagata Kumiko Tokuda Tomoko Horisawa Kazuto Yamazaki 《Neurochemistry international》2012
Lurasidone is a novel antipsychotic agent with high affinity for dopamine D2, 5-hydroxyltryptamine 5-HT2A, and 5-HT7 receptors. Lurasidone has negligible affinity for histamine H1 and muscarinic M1 receptors, which are thought to contribute to side effects such as weight gain, sedation, and worsening of cognitive deficits. Our interests focus on why lurasidone has such high selectivity for only a part of these aminergic G-protein coupled receptors (GPCRs) and the different binding profile from ziprasidone, which has the same benzisothiazolylpiperazine moiety as lurasidone. In order to address these issues, we constructed structural models of lurasidone–GPCR complexes by homology modeling of receptors, exhaustive docking of ligand, and molecular dynamics simulation-based refinement of complexes. This computational study gave reliable structural models for D2, 5-HT2A, and 5-HT7, which had overall structural complementarities with a salt bridge anchor at the center of the lurasidone molecule, but not for H1 and M1 owing to steric hindrance between the norbornane-2,3-dicarboximide and/or cyclohexane part of lurasidone and both receptors. By comparison with the structural models of olanzapine–GPCRs and ziprasidone–GPCRs constructed using the same computational protocols, it was suggested that the bulkiness of the norbornane-2,3-dicarboximide part and the rigidity and the bulkiness of the cyclohexyl linker gave lurasidone high selectivity for the desired aminergic GPCRs. Finally, this structural insight was validated by a binding experiment of the novel benzisothiazolylpiperazine derivatives. This knowledge on the structural mechanism behind the receptor selectivity should help to design new antipsychotic agents with preferable binding profiles, and the established computational protocols realize virtual screening and structure-based drug design for other central nervous system drugs with desired selectivity for multiple targets. 相似文献