全文获取类型
收费全文 | 1554篇 |
免费 | 116篇 |
国内免费 | 2篇 |
专业分类
1672篇 |
出版年
2023年 | 2篇 |
2022年 | 9篇 |
2021年 | 15篇 |
2020年 | 14篇 |
2019年 | 18篇 |
2018年 | 19篇 |
2017年 | 14篇 |
2016年 | 21篇 |
2015年 | 47篇 |
2014年 | 60篇 |
2013年 | 77篇 |
2012年 | 86篇 |
2011年 | 86篇 |
2010年 | 53篇 |
2009年 | 54篇 |
2008年 | 92篇 |
2007年 | 99篇 |
2006年 | 91篇 |
2005年 | 106篇 |
2004年 | 95篇 |
2003年 | 95篇 |
2002年 | 98篇 |
2001年 | 47篇 |
2000年 | 31篇 |
1999年 | 50篇 |
1998年 | 30篇 |
1997年 | 21篇 |
1996年 | 15篇 |
1995年 | 16篇 |
1994年 | 15篇 |
1993年 | 8篇 |
1992年 | 20篇 |
1991年 | 14篇 |
1990年 | 16篇 |
1989年 | 17篇 |
1988年 | 23篇 |
1987年 | 9篇 |
1986年 | 22篇 |
1985年 | 7篇 |
1984年 | 12篇 |
1983年 | 11篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1977年 | 5篇 |
1976年 | 7篇 |
1974年 | 4篇 |
1971年 | 3篇 |
1967年 | 1篇 |
排序方式: 共有1672条查询结果,搜索用时 0 毫秒
171.
Naoki Kubo Hidehiro Toh Kenjiro Shirane Takayuki Shirakawa Hisato Kobayashi Tetsuya Sato Hidetoshi Sone Yasuyuki Sato Shin-ichi Tomizawa Yoshinori Tsurusaki Hiroki Shibata Hirotomo Saitsu Yutaka Suzuki Naomichi Matsumoto Mikita Suyama Tomohiro Kono Kazuyuki Ohbo Hiroyuki Sasaki 《BMC genomics》2015,16(1)
172.
Connective tissue growth factor is required for normal follicle development and ovulation 总被引:1,自引:0,他引:1
Nagashima T Kim J Li Q Lydon JP DeMayo FJ Lyons KM Matzuk MM 《Molecular endocrinology (Baltimore, Md.)》2011,25(10):1740-1759
Connective tissue growth factor (CTGF) is a cysteine-rich protein the synthesis and secretion of which are hypothesized to be selectively regulated by activins and other members of the TGF-β superfamily. To investigate the in vivo roles of CTGF in female reproduction, we generated Ctgf ovarian and uterine conditional knockout (cKO) mice. Ctgf cKO mice exhibit severe subfertility and multiple reproductive defects including disrupted follicle development, decreased ovulation rates, increased numbers of corpus luteum, and smaller but functionally normal uterine horns. Steroidogenesis is disrupted in the Ctgf cKO mice, leading to increased levels of serum progesterone. We show that disrupted follicle development is accompanied by a significant increase in granulosa cell apoptosis. Moreover, despite normal cumulus expansion, Ctgf cKO mice exhibit a significant decrease in oocytes ovulated, likely due to impaired ovulatory process. During analyses of mRNA expression, we discovered that Ctgf cKO granulosa cells show gene expression changes similar to our previously reported granulosa cell-specific knockouts of activin and Smad4, the common TGF-β family intracellular signaling protein. We also discovered a significant down-regulation of Adamts1, a progesterone-regulated gene that is critical for the remodeling of extracellular matrix surrounding granulosa cells of preovulatory follicles. These findings demonstrate that CTGF is a downstream mediator in TGF-β and progesterone signaling cascades and is necessary for normal follicle development and ovulation. 相似文献
173.
Inoue H Iihara A Takahashi H Shimada I Ishida I Maeda Y 《Protein science : a publication of the Protein Society》2011,20(12):1971-1981
VHH is the binding domain of the IgG heavy chain. Some VHHs have an extremely long CDR3 that contributes to antigen binding. We studied the antigen binding ability of CDR3 by grafting a CDR3 from an antigen-binding VHH onto a nonbinding VHH. cAb-CA05-(1RI8), the CDR3-grafted VHH, had an antigen-binding ability. To find a human scaffold protein acceptable for VHH CDR3 grafting, we focused on the conserved structure of VHH, especially the N-terminal and C-terminal amino acid residues of the CDR3 loop and the Cys residue of CDR1. Human origin protein structures with the same orientation were searched in PDB and ubiquitin was selected. Ubi-(1RI8), the CDR3-grafted ubiquitin, had antigen-binding ability, though the affinity was relatively low compared to cAb-CA05-(1RI8). The thermodynamic parameters of Ubi-(1RI8) binding to HEWL were different from cAb-CA05-(1RI8). Hydrogen-deuterium exchange experiments showed decreased stability around the CDR3 grafting region of Ubi-(1RI8), which might explain the decreased antigen-binding ability and the differences in thermodynamic properties. We concluded that the orientation of the CDR3 sequence of Ubi-(1RI8) could not be reconstructed correctly. 相似文献
174.
Ayumu Sugiura Ryo Yonashiro Toshifumi Fukuda Nobuko Matsushita Shun Nagashima Ryoko Inatome Shigeru Yanagi 《Mitochondrion》2011,11(1):139-146
Expansion of a polyglutamine tract in ataxin-3 (polyQ) causes Machado–Joseph disease, a late-onset neurodegenerative disorder characterized by ubiquitin-positive aggregate formation. Several lines of evidence demonstrate that polyQ also accumulates in mitochondria and causes mitochondrial dysfunction. To uncover the mechanism of mitochondrial quality-control via the ubiquitin–proteasome pathway, we investigated whether MITOL, a novel mitochondrial ubiquitin ligase localized in the mitochondrial outer membrane, is involved in the degradation of pathogenic ataxin-3 in mitochondria. In this study, we used N-terminal-truncated pathogenic ataxin-3 with a 71-glutamine repeat (ΔNAT-3Q71) and found that MITOL promoted ΔNAT-3Q71 degradation via the ubiquitin–proteasome pathway and attenuated mitochondrial accumulation of ΔNAT-3Q71. Conversely, MITOL knockdown induced an accumulation of detergent-insoluble ΔNAT-3Q71 with large aggregate formation, resulting in cytochrome c release and subsequent cell death. Thus, MITOL plays a protective role against polyQ toxicity, and thereby may be a potential target for therapy in polyQ diseases. Our findings indicate a protein quality-control mechanism at the mitochondrial outer membrane via a MITOL-mediated ubiquitin–proteasome pathway. 相似文献
175.
176.
Although evidence for the evolution of terrestrial species on islands continues to rapidly accumulate, little is known about the evolution of marine species in geographically isolated environments such as islands as ocean currents often facilitate gene flow among populations. In this study, we focused on marine lakes of the Palau Islands, which are considered to be true analogues of terrestrial islands for marine species. To examine evolutionary processes in marine lakes, we conducted population genetic analyses on marine lake and lagoon populations of the striped silverside, Atherinomorus endrachtensis, using two mitochondrial DNA markers differing in evolutionary rate, the cytochrome b gene and the control region. The analyses revealed that the amount of genetic diversity of marine lake populations is much lower than that of lagoon populations and high levels of genetic differentiation occur among marine lake and lagoon populations. The present study has shown that marine lake populations have been completely isolated and have differentiated from lagoon populations, and each marine lake population is experiencing different evolutionary processes. These findings clearly demonstrate that marine lakes are excellent environments for the evolutionary study of marine species. 相似文献
177.
Ciliates and flagellates temporarily swim backwards on collision by generating a mechanoreceptor potential. Although this potential has been shown to be associated with cilia in Paramecium, the molecular entity of the mechanoreceptor has remained unknown. Here we show that Chlamydomonas cells express TRP11, a member of the TRP (transient receptor potential) subfamily V, in the proximal region of the flagella, and that suppression of TRP11 expression results in loss of the avoiding reaction. The results indicate that Chlamydomonas flagella exhibit mechanosensitivity, despite constant motility, by localizing the mechanoreceptor in the proximal region, where active bending is restricted. 相似文献
178.
Yuko Haida Shigaku Ikeda Atsushi Takagi Etsuko Komiyama Tomotaka Mabuchi Akira Ozawa Jerzy K. Kulski Hidetoshi Inoko Akira Oka 《Immunogenetics》2013,65(7):553-557
Alopecia areata (AA) is an organ-specific and cell-mediated autoimmune disease involving hair loss, but its pathogenesis remains poorly understood. Many autoimmune diseases are genetically associated with alleles of the human leukocyte antigen (HLA) genes within the major histocompatibility complex. Associations between AA and HLA genes were previously observed in some different ethnic groups. However, the results were inconsistent, and a primary susceptibility HLA gene and/or region has not yet been assigned for AA. The aim of this study was to evaluate whether an allele of the HLA-C locus, HLA-C*07:04, which was strongly associated with AA in Chinese Hans, could be replicated in the Japanese population. The HLA-C locus was genotyped by the SSO method using 156 AA patients and 560 healthy controls. As a consequence, among the 17 alleles detected, only two alleles, C*04:01 (OR?=?2.25, CI 95 %?=?1.35–3.75, P?=?1.84E-03) and C*15:02 (OR?=?2.52, CI 95 %?=?1.37–4.64, P?=?2.90E-03), were significantly associated with AA after Bonferroni correction. Further, the stratification analysis suggested that C*04:01, C*07:02, and C*15:02 represented different AA genetic risk factors in each sub-phenotype. 相似文献
179.
180.
Position of single amino acid substitutions in the collagen triple helix determines their effect on structure of collagen fibrils 总被引:4,自引:0,他引:4
Steplewski A Ito H Rucker E Brittingham RJ Alabyeva T Gandhi M Ko FK Birk DE Jimenez SA Fertala A 《Journal of structural biology》2004,148(3):674-337
Collagen II fibrils are a critical structural component of the extracellular matrix of cartilage providing the tissue with its unique biomechanical properties. The self-assembly of collagen molecules into fibrils is a spontaneous process that depends on site-specific binding between specific domains belonging to interacting molecules. These interactions can be altered by mutations in the COL2A1 gene found in patients with a variety of heritable cartilage disorders known as chondrodysplasias. Employing recombinant procollagen II, we studied the effects of R75C or R789C mutations on fibril formation. We determined that both R75C and R789C mutants were incorporated into collagen assemblies. The effects of the R75C and R789C substitutions on fibril formation differed significantly. The R75C substitution located in the thermolabile region of collagen II had no major effect on the fibril formation process or the morphology of fibrils. In contrast, the R789C substitution located in the thermostable region of collagen II caused profound changes in the morphology of collagen assemblies. These results provide a basis for identifying pathways leading from single amino acid substitutions in collagen II to changes in the structure of individual fibrils and in the organization of collagenous matrices. 相似文献