全文获取类型
收费全文 | 3191篇 |
免费 | 203篇 |
出版年
2022年 | 18篇 |
2021年 | 27篇 |
2020年 | 17篇 |
2019年 | 19篇 |
2018年 | 29篇 |
2017年 | 20篇 |
2016年 | 42篇 |
2015年 | 82篇 |
2014年 | 88篇 |
2013年 | 158篇 |
2012年 | 161篇 |
2011年 | 156篇 |
2010年 | 93篇 |
2009年 | 99篇 |
2008年 | 175篇 |
2007年 | 172篇 |
2006年 | 137篇 |
2005年 | 168篇 |
2004年 | 173篇 |
2003年 | 182篇 |
2002年 | 157篇 |
2001年 | 96篇 |
2000年 | 79篇 |
1999年 | 78篇 |
1998年 | 51篇 |
1997年 | 44篇 |
1996年 | 25篇 |
1995年 | 32篇 |
1994年 | 25篇 |
1993年 | 32篇 |
1992年 | 73篇 |
1991年 | 49篇 |
1990年 | 55篇 |
1989年 | 66篇 |
1988年 | 49篇 |
1987年 | 44篇 |
1986年 | 35篇 |
1985年 | 42篇 |
1984年 | 30篇 |
1983年 | 16篇 |
1982年 | 21篇 |
1981年 | 21篇 |
1979年 | 21篇 |
1978年 | 16篇 |
1974年 | 18篇 |
1973年 | 25篇 |
1971年 | 16篇 |
1968年 | 18篇 |
1967年 | 20篇 |
1966年 | 17篇 |
排序方式: 共有3394条查询结果,搜索用时 15 毫秒
141.
Takafumi Nakagawa Yasuo Shikamoto Hiroshi Mizuno Tadashi Murase Hajime Ishii Toru Nakabayashi 《Journal of biomolecular structure & dynamics》2013,31(3):203-207
Abstract Molecular dynamics simulations of the protein C γ-carboxyglutamic acid (Gla) domain and endothelial cell protein C receptor (EPCR) complex were performed to determine the effect of a hereditary disease, which results in a mutation (Gla 25 → Lys) in the protein C Gla domain. Our results suggest that the Gla 25 → Lys mutation causes a significant reduction in the binding force between protein C Gla domain and EPCR due to destabilization of the helix structure of EPCR and displacement of a Ca2+ ion. 相似文献
142.
Saori Umeki Ryoichi Suzuki Yasuo Ema Masayuki Shimojima Yorihiro Nishimura Masaru Okuda Takuya Mizuno 《Journal of cellular biochemistry》2013,114(6):1271-1285
P‐selectin glycoprotein ligand‐1 (PSGL‐1) is an adhesive molecule that is known to be a ligand for P‐selectin. An anti‐adhesive property of PSGL‐1 has not been previously reported. In this study, we show that PSGL‐1 expression is anti‐adhesive for adherent cells and we have elucidated the underlying mechanism. Overexpression of PSGL‐1 induced cell rounding and floating in HEK293T cells. Similar phenomena were demonstrated in other adherent cell lines with overexpression of PSGL‐1. PSGL‐1 overexpression inhibits access of antibodies to cell surface molecules such as integrins, HLA and CD25. Cells transfected with PSGL‐1 deletion mutants that lack a large part of the extracellular domain and chimeric construct expressing extracellular CD86 and intracellular PSGL‐1 only showed rounded morphology, but there are no floating cells. These results indicated that PSGL‐1 causes steric hindrance due to the extended structure of its extracellular domain that is highly O‐glycosylated, but intracellular domain also has some effect on cell rounding. This study implies that PSGL‐1 has Janus‐faced functions, being both adhesive and anti‐adhesive. J. Cell. Biochem. 114: 1271–1285, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
143.
Takayuki Shojima Rokusuke Yoshikawa Shigeki Hoshino Sayumi Shimode So Nakagawa Takuji Ohata Rie Nakaoka Takayuki Miyazawa 《Journal of virology》2013,87(17):9943-9948
We identified a new subgroup of koala retrovirus (KoRV), named KoRV-J, which utilizes thiamine transport protein 1 as a receptor instead of the Pit-1 receptor used by KoRV (KoRV-A). By subgroup-specific PCR, KoRV-J and KoRV-A were detected in 67.5 and 100% of koalas originating from koalas from northern Australia, respectively. Altogether, our results indicate that the invasion of the koala population by KoRV-J may have occurred more recently than invasion by KoRV-A. 相似文献
144.
Elena Pokidysheva Keith D. Zientek Yoshihiro Ishikawa Kazunori Mizuno Janice A. Vranka Nathan T. Montgomery Douglas R. Keene Tatsuya Kawaguchi Kenji Okuyama Hans Peter B?chinger 《The Journal of biological chemistry》2013,288(34):24742-24752
Type I collagen extracted from tendon, skin, and bone of wild type and prolyl 3-hydroxylase 1 (P3H1) null mice shows distinct patterns of 3-hydroxylation and glycosylation of hydroxylysine residues. The A1 site (Pro-986) in the α1-chain of type I collagen is almost completely 3-hydroxylated in every tissue of the wild type mice. In contrast, no 3-hydroxylation of this proline residue was found in P3H1 null mice. Partial 3-hydroxylation of the A3 site (Pro-707) was present in tendon and bone, but absent in skin in both α-chains of the wild type animals. Type I collagen extracted from bone of P3H1 null mice shows a large reduction in 3-hydroxylation of the A3 site in both α-chains, whereas type I collagen extracted from tendon of P3H1 null mice shows little difference as compared with wild type. These results demonstrate that the A1 site in type I collagen is exclusively 3-hydroxylated by P3H1, and presumably, this enzyme is required for the 3-hydroxylation of the A3 site of both α-chains in bone but not in tendon. The increase in glycosylation of hydroxylysine in P3H1 null mice in bone was found to be due to an increased occupancy of normally glycosylated sites. Despite the severe disorganization of collagen fibrils in adult tissues, the D-period of the fibrils is unchanged. Tendon fibrils of newborn P3H1 null mice are well organized with only a slight increase in diameter. The absence of 3-hydroxyproline and/or the increased glycosylation of hydroxylysine in type I collagen disturbs the lateral growth of the fibrils. 相似文献
145.
Masakazu Atobe Kenji Naganuma Masashi Kawanishi Akifumi Morimoto Ken-ichi Kasahara Shigeki Ohashi Hiroko Suzuki Takahiko Hayashi Shiro Miyoshi 《Bioorganic & medicinal chemistry letters》2013,23(22):6064-6067
We describe a medicinal chemistry approach to generate a series of 2-(1H-pyrazol-1-yl)thiazole compounds that act as selective EP1 receptor antagonists. The obtained results suggest that compound 12 provides the best EP1 receptor antagonist activity and demonstrates good oral pharmacokinetics. 相似文献
146.
Takahide Saito Naomichi Iso Haruo Mizuno Hiroo Kanhda Yoshio Suyama Shirô Kawamura 《Bioscience, biotechnology, and biochemistry》2013,77(10):1941-1946
The mucin obtained from a natto sample was found to be composed of 58 % of γ-polyglutamic acid and 40% of polysaccharide. The ratio of l- and d-glutamic acid was determined to be 58:42 using l-glutamic acid decarboxylase. The weight- and z-average molecular weight were 2.08 × 105 and 2.22 × 105, respectively. The distribution curve of the sedimentation coefficient showed a small heterogeneity. The mucin molecule was considered to be randomly coiled at pH 5.0 ~ 8.8 and to be a rod-like molecule in the lower pH region. 相似文献
147.
Hiroto Nishijima Kouichi Nozaki Masahiro Mizuno Tsutomu Arai 《Bioscience, biotechnology, and biochemistry》2013,77(5):738-746
The xylanase (Xyn10B) that strongly adsorbs on microcrystalline cellulose was isolated from Driselase. The Xyn10B contains a Carbohydrate-binding module family 1 (CBM1) (IrpCBMXyn10B) at N-terminus. The canonical essential aromatic residues required for cellulose binding were conserved in IrpCBMXyn10B; however, its adsorption ability was markedly higher than that typically observed for the CBM1 of an endoglucanase from Trametes hirsuta (ThCBMEG1). An analysis of the CBM-GFP fusion proteins revealed that the binding capacity to cellulose (7.8 μmol/g) and distribution coefficient (2.0 L/μmol) of IrpCBMXyn10B-GFP were twofold higher than those of ThCBMEG1-GFP (3.4 μmol/g and 1.2 L/μmol, respectively), used as a reference structure. Besides the canonical aromatic residues (W24-Y50-Y51) of typical CBM1-containing proteins, IrpCBMXyn10B had an additional aromatic residue (Y52). The mutation of Y52 to Ser (IrpCBMY52S-GFP) reduced these adsorption parameters to 4.4 μmol/g and 1.5 L/μmol, which were similar to those of ThCBMEG1-GFP. These results indicate that Y52 plays a crucial role in strong cellulose binding. 相似文献
148.
Sanae Haga YiMin Hikari Yamaki Shigeki Jin Tetsuya Sogon 《Bioscience, biotechnology, and biochemistry》2013,77(11):2110-2120
ABSTRACTBilberry has been reported to have anti-oxidant and anti-inflammatory properties. We studied the effect of bilberry (Vaccinium myrtillus L.) fruits extracts (BEs) on the pathogenesis caused by lipid accumulation in fatty liver and non-alcoholic steatohepatitis (NASH). 5 μg/ml of BEs was enough to suppress lipid accumulation in the fatty liver model of the mouse hepatic AML12 cells. BEs increased cell viability and anti-oxidant capacity, presumably by activating (phosphorylating) Akt/STAT3 and inducing MnSOD/catalase. BEs also significantly reduced Rubicon and induced p62/SQSTM1, possibly contributing to reduce cellular lipids (lipophagy). When the mice were fed supplemented with BEs (5% or 10%, w/w), hepatic steatosis, injury, and hypercholesterolemia/hyperglycemia were significantly improved. Furthermore, histological and cytokine studies indicated that BEs possibly suppress hepatic inflammation (hepatitis) and fibrosis. Therefore, BEs improved liver steatosis and injury, and potentially suppress fibrosis by suppressing inflammatory response, which therefore may prevent the progression of fatty liver to NASH. 相似文献
149.
150.
Yusuke Tani Keisuke Araki Takehiro Nagai Kowa Koida Shigeki Nakauchi Michiteru Kitazaki 《PloS one》2013,8(1)
It has been argued that when an observer moves, a contingent retinal-image motion of a stimulus would strengthen the perceived glossiness. This would be attributed to the veridical perception of three-dimensional structure by motion parallax. However, it has not been investigated whether the effect of motion parallax is more than that of retinal-image motion of the stimulus. Using a magnitude estimation method, we examine in this paper whether cross-modal coordination of the stimulus change and the observer''s motion (i.e., motion parallax) is essential or the retinal-image motion alone is sufficient for enhancing the perceived glossiness. Our data show that a retinal-image motion simulating motion parallax without head motion strengthened the perceived glossiness but that its effect was weaker than that of motion parallax with head motion. These results suggest the existence of an additional effect of the cross-modal coordination between vision and proprioception on glossiness perception. That is, motion parallax enhances the perception of glossiness, in addition to retinal-image motions of specular surfaces. 相似文献