全文获取类型
收费全文 | 298篇 |
免费 | 10篇 |
出版年
2022年 | 5篇 |
2021年 | 9篇 |
2020年 | 5篇 |
2019年 | 5篇 |
2018年 | 10篇 |
2017年 | 9篇 |
2016年 | 7篇 |
2015年 | 14篇 |
2014年 | 12篇 |
2013年 | 10篇 |
2012年 | 29篇 |
2011年 | 21篇 |
2010年 | 10篇 |
2009年 | 12篇 |
2008年 | 25篇 |
2007年 | 20篇 |
2006年 | 16篇 |
2005年 | 12篇 |
2004年 | 15篇 |
2003年 | 14篇 |
2002年 | 11篇 |
2001年 | 3篇 |
2000年 | 2篇 |
1998年 | 5篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1982年 | 4篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
排序方式: 共有308条查询结果,搜索用时 31 毫秒
221.
Nao Hosokawa Taichi Hara Takeshi Kaizuka Chieko Kishi Akito Takamura Yutaka Miura Shun-ichiro Iemura Tohru Natsume Kenji Takehana Naoyuki Yamada Jun-Lin Guan Noriko Oshiro Noboru Mizushima 《Molecular biology of the cell》2009,20(7):1981-1991
Autophagy is an intracellular degradation system, by which cytoplasmic contents are degraded in lysosomes. Autophagy is dynamically induced by nutrient depletion to provide necessary amino acids within cells, thus helping them adapt to starvation. Although it has been suggested that mTOR is a major negative regulator of autophagy, how it controls autophagy has not yet been determined. Here, we report a novel mammalian autophagy factor, Atg13, which forms a stable ~3-MDa protein complex with ULK1 and FIP200. Atg13 localizes on the autophagic isolation membrane and is essential for autophagosome formation. In contrast to yeast counterparts, formation of the ULK1–Atg13–FIP200 complex is not altered by nutrient conditions. Importantly, mTORC1 is incorporated into the ULK1–Atg13–FIP200 complex through ULK1 in a nutrient-dependent manner and mTOR phosphorylates ULK1 and Atg13. ULK1 is dephosphorylated by rapamycin treatment or starvation. These data suggest that mTORC1 suppresses autophagy through direct regulation of the ~3-MDa ULK1–Atg13–FIP200 complex. 相似文献
222.
223.
Caldecrin was originally isolated from the pancreas as afactor that reduced serum calcium levels. This secreted serine protease has chymotrypsin-like activity and is also known as chymotrypsin C; it belongs to the elastase family. Although intravenous administration of caldecrin decreases the serum calcium concentration even when its protease activity is blocked,this effect does require cleavage of caldecrin's pro-peptide by trypsin,converting it to the mature enzyme. Ectopic intramuscular expression of caldecrin prevented bone resorption in ovariectomized mice. Caldecrin inhibited parathyroid hormone-stimulated calcium release from fetal mouse long bone organ cultures. Furthermore,caldecrin suppressed the formation of osteoclasts from bone marrow cells by inhibiting the receptor activator of nuclear factor-k B ligand(RANKL)-stimulated phospholipase Cγ-calcium oscillation-calcineurinnuclear factor of activated T-cells,cytoplasmic 1 pathway. Caldecrin also suppressed the bone resorption activity of mature osteoclasts by preventing RANKL-stimulated Src activation,calcium entry,and actin ring formation. In vivo and in vitro studies have indicated that caldecrin is a unique multifunctional protease with anti-osteoclastogenic activities that are distinct from its protease activity. Caldecrin might be a potential therapeutic target for the treatment of osteolytic diseases such as osteoporosis and osteoarthritis. This mini-review describes caldecrin's historical background and its mechanisms of action. 相似文献
224.
Daisuke Kawahara Shuichi Ozawa Akito Saito Yasushi Nagata 《Reports of Practical Oncology and Radiotherapy》2022,27(5):848
BackgroundThe effective atomic numbers obtained from dual-energy computed tomography (DECT) can aid in characterization of materials. In this study, an effective atomic number image reconstructed from a DECT image was synthesized using an equivalent single-energy CT image with a deep convolutional neural network (CNN)-based generative adversarial network (GAN).Materials and methodsThe image synthesis framework to obtain the effective atomic number images from a single-energy CT image at 120 kVp using a CNN-based GAN was developed. The evaluation metrics were the mean absolute error (MAE), relative root mean square error (RMSE), relative mean square error (MSE), structural similarity index (SSIM), peak signal-to-noise ratio (PSNR), and mutual information (MI).ResultsThe difference between the reference and synthetic effective atomic numbers was within 9.7% in all regions of interest. The averages of MAE, RMSE, MSE, SSIM, PSNR, and MI of the reference and synthesized images in the test data were 0.09, 0.045, 0.0, 0.89, 54.97, and 1.03, respectively.ConclusionsIn this study, an image synthesis framework using single-energy CT images was constructed to obtain atomic number images scanned by DECT. This image synthesis framework can aid in material decomposition without extra scans in DECT. 相似文献
225.
Atsushi Sanbe Tetsuro Marunouchi Tsutomu Abe Yu Tezuka Mizuki Okada Sayuri Aoki Hideki Tsumura Junji Yamauchi Kouichi Tanonaka Hideo Nishigori Akito Tanoue 《The Journal of biological chemistry》2013,288(13):8910-8921
A K141N missense mutation in heat shock protein (HSP) B8, which belongs to the small HSP family, causes distal hereditary motor neuropathy, which is characterized by the formation of inclusion bodies in cells. Although the HSPB8 gene causes hereditary motor neuropathy, obvious expression of HSPB8 is also observed in other tissues, such as the heart. The effects of a single mutation in HSPB8 upon the heart were analyzed using rat neonatal cardiomyocytes. Expression of HSPB8 K141N by adenoviral infection resulted in increased HSPB8-positive aggregates around nuclei, whereas no aggregates were observed in myocytes expressing wild-type HSPB8. HSPB8-positive aggresomes contained amyloid oligomer intermediates that were detected by a specific anti-oligomer antibody (A11). Expression of HSPB8 K141N induced slight cellular toxicity. Recombinant HSPB8 K141N protein showed reactivity against the anti-oligomer antibody, and reactivity of the mutant HSPB8 protein was much higher than that of wild-type HSPB8 protein. To extend our in vitro study, cardiac-specific HSPB8 K141N transgenic (TG) mice were generated. Echocardiography revealed that the HSPB8 K141N TG mice exhibited mild hypertrophy and apical fibrosis as well as slightly reduced cardiac function, although no phenotype was detected in wild-type HSPB8 TG mice. A single point mutation of HSPB8, such as K141N, can cause cardiac disease. 相似文献
226.
Keita Fukui Kei Nanatani Yoshihiko Hara Suguru Yamakami Daiki Yahagi Akito Chinen 《Bioscience, biotechnology, and biochemistry》2017,81(9):1837-1844
Under anaerobic conditions, Escherichia coli produces succinate from glucose via the reductive tricarboxylic acid cycle. To date, however, no genes encoding succinate exporters have been established in E. coli. Therefore, we attempted to identify genes encoding succinate exporters by screening an E. coli MG1655 genome library. We identified the yjjPB genes as candidates encoding a succinate transporter, which enhanced succinate production in Pantoea ananatis under aerobic conditions. A complementation assay conducted in Corynebacterium glutamicum strain AJ110655ΔsucE1 demonstrated that both YjjP and YjjB are required for the restoration of succinate production. Furthermore, deletion of yjjPB decreased succinate production in E. coli by 70% under anaerobic conditions. Taken together, these results suggest that YjjPB constitutes a succinate transporter in E. coli and that the products of both genes are required for succinate export. 相似文献
227.
Shigeo Takagi Takao Yoshida Atsushi Ohya Katsuo Tsubata Hisae Sakata Kiyoshi T. Fujii Sadao Iizuka Buichi Tochigi Meijin Tochigi Akito Mochigi 《Prostaglandins & other lipid mediators》1982,23(4):591-601
The present clinical trials revealed that 16,16-Dimethyl-trans-δ2-PGE1 methyl ester in the form of vaginal suppositories is highly effective in inducing mid-trimester termination of pregnancies. It also showed that prior treatment with laminaria and metreurynter may enhance the success rate while reducing the incidence and severity of side effects. It is easy and safe to use clinically, with minimal side effects, and in our series, revealed no deleterious effects on ensuing reproductive physiology. However, the definite mechanism involved in the action of this new analogue to cause myometrial contractions is still not completely understood, and requires further intensive investigation. 相似文献
228.
H Nakayama S Taneda S Aoki K Komori Y Kuroda K Misawa S Tsushima S Nakagawa 《Biochemical and biophysical research communications》1985,131(2):720-725
The existence of antibodies to nonenzymatically glucosylated albumin was investigated in nondiabetic and diabetic subjects. The sera from both the nondiabetic and the diabetic subjects were shown to contain the proteins which bound to reductively glucosylated albumin. An enzyme-linked immunosorbent assay demonstrated that the antibodies specific for reductively glucosylated albumin existed in the sera containing the binding proteins. For binding the antibodies glucitollysine as the glucose adduct in reductively glucosylated albumin was an effective competitor. The hexose alcohol epimers glucitol and mannitol were also effective competitors compatible with glucitollysine. Our results suggest that the antibodies to reductively glucosylated albumin are widely present not only in the diabetic subjects but also in the nondiabetic subjects and cross-react with the hexose alcohol. 相似文献
229.
230.
Maachi Kataoka Akito Yamaoka Kazunori Kawasaki Yasushi Shigeri Kunihiko Watanabe 《Applied microbiology and biotechnology》2014,98(7):2973-2980
A moderately thermophilic bacterial strain, Meiothermus ruber H328, can efficiently solubilize intact chicken feathers by aerobic cultivation at 55 °C for 6 days. The keratinolytic proteases extracellularly secreted by the strain were partially purified by an ultrafiltration system and a size-exclusion column chromatography, and thus were found to be two different sizes of macromolecules with an extremely high molecular mass like the sizes of virus and DNA (peak 1 fraction) and with a molecular mass of larger than 500 kDa (peak 2 fraction). They formed protein complex assemblies that were composed of multiple but different proteins. The peak 1 fraction showed more thermophilic characteristics than did the peak 2 fraction in temperature dependence and thermal stability. By contrast, they comparably showed extraordinary resistance to powerful denaturants, SDS at 30 % (w/v) and organic solvents (methanol, ethanol, acetonitrile, acetone, and chloroform) at 40 % (v/v) at 60 °C for 30 min. The extraordinary denaturant tolerance and the large molecular size of the keratinolytic protease complex assemblies suggest the possibility that those may be lipophilic and have the structure of partial membrane fractions, or membrane vesicles, which are exfoliated from the outer membrane of the cells. 相似文献