全文获取类型
收费全文 | 1720篇 |
免费 | 99篇 |
出版年
2023年 | 5篇 |
2022年 | 4篇 |
2021年 | 22篇 |
2020年 | 8篇 |
2019年 | 14篇 |
2018年 | 21篇 |
2017年 | 15篇 |
2016年 | 24篇 |
2015年 | 52篇 |
2014年 | 60篇 |
2013年 | 80篇 |
2012年 | 90篇 |
2011年 | 90篇 |
2010年 | 48篇 |
2009年 | 64篇 |
2008年 | 94篇 |
2007年 | 92篇 |
2006年 | 73篇 |
2005年 | 115篇 |
2004年 | 104篇 |
2003年 | 103篇 |
2002年 | 96篇 |
2001年 | 63篇 |
2000年 | 78篇 |
1999年 | 46篇 |
1998年 | 20篇 |
1997年 | 23篇 |
1996年 | 20篇 |
1995年 | 22篇 |
1994年 | 19篇 |
1993年 | 17篇 |
1992年 | 24篇 |
1991年 | 35篇 |
1990年 | 20篇 |
1989年 | 19篇 |
1988年 | 20篇 |
1987年 | 22篇 |
1986年 | 11篇 |
1985年 | 18篇 |
1984年 | 4篇 |
1983年 | 9篇 |
1982年 | 11篇 |
1981年 | 5篇 |
1979年 | 5篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1972年 | 5篇 |
1969年 | 2篇 |
1966年 | 2篇 |
1965年 | 2篇 |
排序方式: 共有1819条查询结果,搜索用时 31 毫秒
41.
Junichi Okuyama Kana Nakajima Takuji Noda Satoko Kimura Hiroko Kamihata Masato Kobayashi Nobuaki Arai Shiro Kagawa Yuuki Kawabata Hideaki Yamada 《PloS one》2013,8(6)
Animals are assumed to obtain/conserve energy effectively to maximise their fitness, which manifests itself in a variety of behavioral strategies. For marine animals, however, these behavioral strategies are generally unknown due to the lack of high-resolution monitoring techniques in marine habitats. As large marine herbivores, immature green turtles do not need to allocate energy to reproduction but are at risk of shark predation, although it is a rare occurrence. They are therefore assumed to select/use feeding and resting sites that maximise their fitness in terms of somatic growth, while avoiding predation. We investigated fine-scale behavioral patterns (feeding, resting and other behaviors), microhabitat use and time spent on each behavior for eight immature green turtles using data loggers including: depth, global positioning system, head acceleration, speed and video sensors. Immature green turtles at Iriomote Island, Japan, spent an average of 4.8 h feeding on seagrass each day, with two peaks, between 5∶00 and 9∶00, and between 17∶00 and 20∶00. This feeding pattern appeared to be restricted by gut capacity, and thus maximised energy acquisition. Meanwhile, most of the remaining time was spent resting at locations close to feeding grounds, which allowed turtles to conserve energy spent travelling and reduced the duration of periods exposed to predation. These behavioral patterns and time allocations allow immature green turtles to effectively obtain/conserve energy for growth, thus maximising their fitness. 相似文献
42.
Susumu Kudo Minoru Kawarabayashi Mariko Ikeda Kazuo Tanishita 《Journal of Biorheology》2013,26(1-2):38-43
Recent studies suggest that the temporal gradient of shear stress that is generated by blood flow plays an important role in the pathology of arteriosclerosis. We focused on the temporal gradient of shear stress and measured the permeability of albumin under steady or pulsatile shear stress conditions. Porcine aortic endothelial cells were seeded on a membrane filter and subjected to steady or pulsatile shear stress (1 Hz) at 1 Pa for 48 h, and the permeability of albumin was measured over time. The permeability increased gradually under steady flow but increased acutely under pulsatile shear stress. In particular, the maximum permeability of albumin differed under these conditions. The value was 4.2 × 10?5 cm/s at 18 h under pulsatile shear stress and 2.8 × 10?5 cm/s at 48 h under steady shear stress. The permeable route of albumin was examined using isoproterenol, which decreases junctional permeability. The increase in albumin permeability with pulsatile shear stress was decreased by isoproterenol. These results suggest that the increased permeability of albumin with pulsatile shear stress was related to trafficking through paracellular junctions. Thus, pulsation may promote a mechanotransduction process that differs from that of steady shear stress, and these pulsation effects likely play an important role in the permeability of macromolecules. 相似文献
43.
44.
Mohammad Badrul Anam Shah Adil Ishtiyaq Ahmad Mikiko Kudo Arif Istiaq Athary Abdulhaleem M. Felemban Naofumi Ito Kunimasa Ohta 《Development, growth & differentiation》2020,62(2):97-107
Specialized microenvironment, or neurogenic niche, in embryonic and postnatal mouse brain plays critical roles during neurogenesis throughout adulthood. The subventricular zone (SVZ) and the dentate gyrus (DG) of hippocampus in the mouse brain are two major neurogenic niches where neurogenesis is directed by numerous regulatory factors. Now, we report Akhirin (AKH), a stem cell maintenance factor in mouse spinal cord, plays a pivotal regulatory role in the SVZ and in the DG. AKH showed specific distribution during development in embryonic and postnatal neurogenic niches. Loss of AKH led to abnormal development of the ventricular zone and the DG along with reduction of cellular proliferation in both regions. In AKH knockout mice (AKH−/−), quiescent neural stem cells (NSCs) increased, while proliferative NSCs or neural progenitor cells decreased at both neurogenic niches. In vitro NSC culture assay showed increased number of neurospheres and reduced neurogenesis in AKH−/−. These results indicate that AKH, at the neurogenic niche, exerts dynamic regulatory role on NSC self-renewal, proliferation and differentiation during SVZ and hippocampal neurogenesis. 相似文献
45.
Naoyuki Okita Miyuki Yoshimura Kazuhito Watanabe Shota Minato Yuki Kudo Yoshikazu Higami Sei-ichi Tanuma 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
CHK1 is an important effector kinase that regulates the cell cycle checkpoint. Previously, we showed that CHK1 is cleaved in a caspase (CASP)-dependent manner during DNA damage-induced programmed cell death (PCD) and have examined its physiological roles.Methods and results
In this study, we investigated the behavior of CHK1 in PCD. Firstly, we found that CHK1 is cleaved at three sites in PCD, and all cleavages were inhibited by the co-treatment of a pan-CASP inhibitor or serine protease inhibitors. We also showed that CHK1 is cleaved by CASP3 and/or CASP7 recognizing at 296SNLD299 and 348TCPD351, and that the cleavage results in the enhancement of CHK1 kinase activity. Furthermore, as a result of the characterization of cleavage sites by site-directed mutagenesis and an analysis performed using deletion mutants, we identified 320EPRT323 as an additional cleavage recognition sequence. Considering the consensus sequence cleaved by CASP, it is likely that CHK1 is cleaved by non-CASP family protease(s) recognizing at 320EPRT323. Additionally, the cleavage catalyzed by the 320EPRT323 protease(s) markedly and specifically increased when U2OS cells synchronized into G1 phase were induced to PCD by cisplatin treatment.Conclusion
CHK1 cleavage is directly and indirectly regulated by CASP and non-CASP family proteases including serine protease(s) and the “320EPRT323 protease(s).” Furthermore, 320EPRT323 cleavage of CHK1 occurs efficiently in PCD which is induced at the G1 phase by DNA damage.General significance
CASP and non-CASP family proteases intricately regulate cleavage for up-regulation of CHK1 kinase activity during PCD. 相似文献46.
Kyosuke Takabe Shuichi Nakamura Masamichi Ashihara Seishi Kudo 《Microbiology and immunology》2013,57(3):236-239
The motility of bacteria is an important factor in their infectivity. In this study, the motility of Leptospira, a member of the spirochete family that causes a zoonotic disease known as leptospirosis, was analyzed in different viscous or osmotic conditions. Motility assays revealed that both pathogenic and saprophytic strains increase their swimming speeds with increasing viscosity. However, only pathogenic Leptospira interrogans maintained vigorous motility near physiological osmotic conditions. This suggests that active motility in physiological conditions is advantageous when Leptospira enters hosts and when it migrates toward target tissues. 相似文献
47.
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
48.
Kyoko Kudo Masaru Ohta Lijun Yang Yuhya Wakasa Sakiko Takahashi Fumio Takaiwa 《Plant molecular biology》2013,81(4-5):461-475
Rice seed has been used as a production platform for high value recombinant proteins. When mature human interleukin 7 (hIL-7) was expressed as a secretory protein in rice endosperm by ligating the N terminal glutelin signal peptide and the C terminal KDEL endoplasmic reticulum (ER) retention signal to the hIL-7 cytokine to improve production yield, this protein accumulated at levels visible by Coomassie Brilliant Blue staining. However, the production of this protein led not only to a severe reduction of endogenous seed storage proteins but also to a deterioration in grain quality. The appearance of aberrant grain phenotypes (such as floury and shrunken) was attributed to ER stress induced by the retention of highly aggregated unfolded hIL-7 in the ER lumen, and the expression levels of chaperones such as BiPs and PDIs were enhanced in parallel with the increase in hIL-7 levels. The activation of this ER stress response was shown to be mainly mediated by the OsIRE1-OsbZIP50 signal cascade, based on the appearance of unconventional splicing of OsbZIP50 mRNA and the induction of OsBiP4&5. Interestingly, the ER stress response could be induced by lower concentrations of hIL-7 versus other types of cytokines such as IL-1b, IL-4, IL-10, and IL-18. Furthermore, several ubiquitin 26S proteasome-related genes implicated in ER-associated degradation were upregulated by hIL-7 production. These results suggest that severe detrimental effects on grain properties were caused by proteo-toxicity induced by unfolded hIL-7 aggregates in the ER, resulting in the triggering of ER stress. 相似文献
49.
Eriko Kudo Manabu Taura Kouki Matsuda Masako Shimamoto Ryusho Kariya Hiroki Goto Shinichiro Hattori Shinya Kimura Seiji Okada 《Bioorganic & medicinal chemistry letters》2013,23(3):606-609
The anti-HIV-1 activity of GUT-70, a natural product derived from the stem bark of Chlophyllum brasiliense, was evaluated. GUT-70 inhibited HIV-1 replication in both acutely and chronically infected cells through suppression of NF-κB. Our results strengthen the idea that NF-κB pathway is one of the potential targets to control HIV-1 replication and that GUT-70 could serve as a lead compound to develop novel therapeutic agents against HIV-1 infection. 相似文献
50.
Shinya Harusawa Koichi Sawada Takuji Magata Hiroki Yoneyama Lisa Araki Yoshihide Usami Kouta Hatano Kouichi Yamamoto Daisuke Yamamoto Atsushi Yamatodani 《Bioorganic & medicinal chemistry letters》2013,23(23):6415-6420
S-Alkyl-N-alkylisothiourea compounds containing various cyclic amines were synthesized in the search for novel nonimidazole histamine H3 receptor (H3R) antagonists. Among them, four N-alkyl S-[3-(piperidin-1-yl)propyl]isothioureas 18, 19, 22, and 23 were found to exhibit potent and selective H3R antagonistic activities against in vitro human H3R, but were inactive against in vitro human H4R. Furthermore, three alkyl homologs 18–20 showed inactivity for histamine release in in vivo rat brain microdialysis, suggesting differences in antagonist affinities between species. In addition, in silico docking studies of N-[4-(4-chlorophenyl)butyl]-S-[3-piperidin-1-yl)propyl]isothiourea 19 and a shorter homolog 17 with human/rat H3Rs revealed that structural differences between the antagonist-docking cavities of rat and human H3Rs were likely caused by the Ala122/Val122 mutation. 相似文献