全文获取类型
收费全文 | 539篇 |
免费 | 27篇 |
出版年
2023年 | 4篇 |
2022年 | 12篇 |
2021年 | 17篇 |
2020年 | 13篇 |
2019年 | 13篇 |
2018年 | 16篇 |
2017年 | 14篇 |
2016年 | 22篇 |
2015年 | 30篇 |
2014年 | 37篇 |
2013年 | 44篇 |
2012年 | 68篇 |
2011年 | 59篇 |
2010年 | 23篇 |
2009年 | 30篇 |
2008年 | 34篇 |
2007年 | 23篇 |
2006年 | 24篇 |
2005年 | 23篇 |
2004年 | 22篇 |
2003年 | 12篇 |
2002年 | 14篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1998年 | 1篇 |
1997年 | 3篇 |
1996年 | 1篇 |
1994年 | 1篇 |
1987年 | 2篇 |
1984年 | 1篇 |
排序方式: 共有566条查询结果,搜索用时 687 毫秒
81.
Onda K Shiraki R Ogiyama T Yokoyama K Momose K Katayama N Orita M Yamaguchi T Furutani M Hamada N Takeuchi M Okada M Ohta M Tsukamoto S 《Bioorganic & medicinal chemistry》2008,16(23):10001-10012
As a result of the various N-bicyclo-5-chloro-1H-indole-2-carboxamide derivatives with a hydroxy moiety synthesized in an effort to discover novel glycogen phosphorylase (GP) inhibitors, 5-chloro-N-(5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-indole-2-carboxamide (5b) was found to have potent inhibitory activity. The introduction of fluorine atoms both at a position adjacent to the hydroxy group and in the central benzene moiety lead to the optically active derivative 5-chloro-N-[(5R)-1,3,6,6-tetrafluoro-5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1H-indole-2-carboxamide (25e(alpha), which was the most potent compound in this series (IC(50)=0.020microM). This compound inhibited glucagon-induced glucose output in cultured primary hepatocytes with an IC(50) value of 0.69microM, and showed oral hypoglycemic activity in diabetic db/db mice at 10mg/kg. Compound 25e(alpha) also had an excellent pharmacokinetic profile, with high oral bioavailability and a long plasma half-life, in male SD rats. The binding mode of 25e(alpha) to this molecule and the role of fluorine atoms in that binding were speculated in an enzyme docking study. 相似文献
82.
83.
Ryota Kataoka Takeshi Taniguchi Kazuyoshi Futai 《World journal of microbiology & biotechnology》2009,25(10):1815-1819
The fungal selectivity of helper effect was revealed using four ectomycorrhizal fungi (Rhizopogon sp., Pisolithus tinctorius, Cenococcum geophilum and Suillus granulatus), and one ectoendomycorrhizal fungus (Wilcoxina mikolae). Previously, we isolated a rhizobacteria, Ralstonia basilensis and Bacillus subtilis, which have the ability to enhance the mycorrhizal symbiosis between S. granulatus and Pinus thunbergii. However, the characteristics of each bacterium on mycorrhizal fungi are still unclear. Therefore, we tried to examine the
fungal selectivity of helper effect. A confrontation assay revealed that R. basilensis significantly promoted the in vitro hyphal growth of W. mikolae and S. granulatus, but it had no effect on Rhizopogon sp., P. tinctorius and C. geophilum. These results were consistent with the effects shown by R. basilensis on the mycorrhizal formation of these fungi. On the other hand, B. subtilis promoted the hyphal growth of W. mikolae and C. geophilum but suppressed growth of Rhizopogon sp. B. subtilis significantly stimulated the mycorrhizal formation of S. granulatus. Thus the effects of B. subtilis on hyphal growth and on mycorrhizal formation were inconsistent. These results suggest that R. basilensis and B. subtilis have fungal selective and different mechanisms in their roles as mycorrhiza helper bacteria. 相似文献
84.
85.
86.
Kohji Mori Shiho Gotoh Tomoko Yamashita Ryota Uozumi Yuya Kawabe Shinji Tagami Frits Kamp Brigitte Nuscher Dieter Edbauer Christian Haass Yoshitaka Nagai Manabu Ikeda 《The Journal of biological chemistry》2021,297(4)
GGGGCC (G4C2) repeat expansion in the C9orf72 gene has been shown to cause frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Dipeptide repeat proteins produced through repeat-associated non-AUG (RAN) translation are recognized as potential drivers for neurodegeneration. Therefore, selective inhibition of RAN translation could be a therapeutic avenue to treat these neurodegenerative diseases. It was previously known that the porphyrin TMPyP4 binds to G4C2 repeat RNA. However, the consequences of this interaction have not been well characterized. Here, we confirmed that TMPyP4 inhibits C9orf72 G4C2 repeat translation in cellular and in in vitro translation systems. An artificial insertion of an AUG codon failed to cancel the translation inhibition, suggesting that TMPyP4 acts downstream of non-AUG translation initiation. Polysome profiling assays also revealed polysome retention on G4C2 repeat RNA, along with inhibition of translation, indicating that elongating ribosomes stall on G4C2 repeat RNA. Urea-resistant interaction between G4C2 repeat RNA and TMPyP4 likely contributes to this ribosome stalling and thus to selective inhibition of RAN translation. Taken together, our data reveal a novel mode of action of TMPyP4 as an inhibitor of G4C2 repeat translation elongation. 相似文献
87.
Ryota Kawanishi Ryota Dohi Asuka Fujii Mikio Inoue Yo Miyake 《Ichthyological Research》2017,64(4):433-443
Vertical hydrological connectivity between the surface stream and benthic and hyporheic zones plays a key ecological role in the biodiversity of lotic ecosystems because it allows surface and benthic organisms to use the hyporheic zone as a seasonal habitat and refuge. Use of the hyporheic zone by surface/benthic organisms has been well studied in invertebrates, but little is known about the importance of this connectivity for fishes. We investigated streambed surface and hyporheic densities (5–10, 15–20 and 20–25 cm below the streambed surface) of a stream fish, Cobitis shikokuensis, over a 20-month period in the Shigenobu River, southwestern Japan, to test the hypothesis that it uses the hyporheic zone for spawning and overwintering. In total, 1,804 individuals (13–58 mm total length) were captured from 33 streambed surface samplings and 102 individuals (10–46 mm total length) were present in 1,147 samples of 57 hyporheic samplings. Population densities in both zones peaked in late summer–early autumn due to the recruitment of age 0+ fish and a female with eggs was found in the hyporheic zone during the reproductive season. Both 0+ and older fish were absent from the streambed surface during winter, and fish densities were also lower in the hyporheic zone at this time. However, the vertical distribution of the fish tended to be skewed towards the deeper hyporheic layers from autumn to spring. These findings indicate that C. shikokuensis vertically migrates between the streambed surface and the hyporheic zone for spawning, rearing and overwintering, suggesting that the integrity of vertical hydrological connectivity in lotic systems is crucial for certain fish species. 相似文献
88.
Junko Tokuno Tsuyoshi Shoji Ryota Sumitomo Yuichiro Ueda Keiji Yamanashi Cheng-long Huang 《World journal of surgical oncology》2017,15(1):212
Background
Video-assisted thoracic surgery (VATS) plays an important role in thoracic surgery because it is less invasive. However, the existence of severe pleural adhesions may make VATS difficult and complicated. The aim of this study was to assess the utility of inspiration and expiration computed tomography (respiratory dynamic CT (RD-CT)) in evaluation of pleural adhesions preoperatively.Methods
RD-CT was performed on 107 patients undergoing thoracotomies (both VATS and open). We assessed synchronous motion during respiration on RD-CT. Comparing the results of RD-CT and intraoperative findings, we assessed the utility of preoperative evaluation.Results
A negative correlation between sliding score and adhesion grade was revealed. Sliding score in adhesion negative patients was significantly higher than that in adhesion positive patients (P?<?0.0001). The sensitivity of RD-CT was 63.6%, specificity was 74.1%, and accuracy was 72%. Among 62 patients with a CT-Respiration Ratio of less than 0.65, the sensitivity of RD-CT was 77.8%, specificity was 86.8%, and accuracy was 85.5%.Conclusions
RD-CT may be clinically useful for detecting the presence of pleural adhesions. It can be adopted as one of the criteria for deciding the surgical approach.89.
Takuya Ikenari Tatsuya Kawaguchi Rei Ota Miki Matsui Ryota Yoshida Tetsuji Mori 《The journal of histochemistry and cytochemistry》2021,69(9):597
Fluoro-Jade C (FJC) staining has been used to detect degenerating neurons in tissue sections. It is a simple and easy staining procedure and does not depend on the manner of cell death. In some experiments, double staining with FJC and fluorescent immunostaining (FI) is required to identify cell types. However, pretreatment for FJC staining contains some processes that are harsh to fluorophores, and the FI signal is greatly reduced. To overcome this issue, we improved the double staining protocol to acquire clear double-stained images by introducing the labeled streptavidin–biotin system. In addition, several studies indicate that FJC can label non-degenerating glial cells, including resting/reactive astrocytes and activated microglia. Moreover, our previous study indicated that degenerating mesenchymal cells were also labeled by FJC, but it is still unclear whether FJC can label degenerating glial cells. Acute encephalopathy model mice contained damaged astrocytes with clasmatodendrosis, and 6-aminonicotinamide-injected mice contained necrotic astrocytes and oligodendrocytes. Using our improved double staining protocol with FJC and FI, we detected FJC-labeled degenerating astrocytes and oligodendrocytes with pyknotic nuclei. These results indicate that FJC is not specific to degenerating neurons in some experimental conditions: 相似文献
90.
Loss of ALS2/alsin function accounts for several recessive motor neuron diseases. ALS2 is a Rab5 activator and its endosomal localization is regulated by Rac1 via macropinocytosis. Here, we show that the pathogenic missense ALS2 mutants fail to be localized to Rac1-induced macropinosomes as well as endosomes, which leads to loss of the ALS2 function as a Rab5 activator on endosomes. Further, these mutants lose the competence to enhance the formation of amphisomes, the hybrid-organelle formed upon fusion between autophagosomes and endosomes. Thus, Rac1-induced relocalization of ALS2 might be crucial to exert the ALS2 function associated with the autophagy-endolysosomal degradative pathway. 相似文献