全文获取类型
收费全文 | 1755篇 |
免费 | 123篇 |
出版年
2022年 | 6篇 |
2021年 | 19篇 |
2020年 | 9篇 |
2019年 | 12篇 |
2018年 | 16篇 |
2017年 | 16篇 |
2016年 | 26篇 |
2015年 | 48篇 |
2014年 | 45篇 |
2013年 | 125篇 |
2012年 | 86篇 |
2011年 | 81篇 |
2010年 | 56篇 |
2009年 | 58篇 |
2008年 | 81篇 |
2007年 | 84篇 |
2006年 | 78篇 |
2005年 | 84篇 |
2004年 | 62篇 |
2003年 | 94篇 |
2002年 | 83篇 |
2001年 | 67篇 |
2000年 | 86篇 |
1999年 | 59篇 |
1998年 | 28篇 |
1997年 | 18篇 |
1996年 | 10篇 |
1995年 | 24篇 |
1994年 | 17篇 |
1993年 | 9篇 |
1992年 | 38篇 |
1991年 | 46篇 |
1990年 | 40篇 |
1989年 | 29篇 |
1988年 | 18篇 |
1987年 | 27篇 |
1986年 | 26篇 |
1985年 | 23篇 |
1984年 | 9篇 |
1983年 | 15篇 |
1982年 | 11篇 |
1981年 | 9篇 |
1980年 | 10篇 |
1979年 | 14篇 |
1978年 | 10篇 |
1977年 | 10篇 |
1976年 | 10篇 |
1975年 | 7篇 |
1974年 | 10篇 |
1971年 | 5篇 |
排序方式: 共有1878条查询结果,搜索用时 15 毫秒
101.
Morita Y Araki H Sugimoto T Takeuchi K Yamane T Maeda T Yamamoto Y Nishi K Asano M Shirahama-Noda K Nishimura M Uzu T Hara-Nishimura I Koya D Kashiwagi A Ohkubo I 《FEBS letters》2007,581(7):1417-1424
Legumain/asparaginyl endopeptidase (EC 3.4.22.34) is a novel cysteine protease that is abundantly expressed in the late endosomes and lysosomes of renal proximal tubular cells. Recently, emerging evidence has indicated that legumain might play an important role in control of extracellular matrix turnover in various pathological conditions such as tumor growth/metastasis and progression of atherosclerosis. We initially found that purified legumain can directly degrade fibronectin, one of the main components of the extracellular matrix, in vitro. Therefore, we examined the effect of legumain on fibronectin degradation in cultured mouse renal proximal tubular cells. Fibronectin processing can be inhibited by chloroquine, an inhibitor of lysosomal degradation, and can be enhanced by the overexpression of legumain, indicating that fibronectin degradation occurs in the presence of legumain in lysosomes from renal proximal tubular cells. Furthermore, in legumain-deficient mice, unilateral ureteral obstruction (UUO)-induced renal interstitial protein accumulation of fibronectin and renal interstitial fibrosis were markedly enhanced. These findings indicate that legumain might have an important role in extracellular matrix remodeling via the degradation of fibronectin in renal proximal tubular cells. 相似文献
102.
Prostaglandin E receptors 总被引:14,自引:0,他引:14
Prostaglandin (PG) E(2) exerts its actions by acting on a group of G-protein-coupled receptors (GPCRs). There are four GPCRs responding to PGE(2) designated subtypes EP1, EP2, EP3, and EP4 and multiple splicing isoforms of the subtype EP3. The EP subtypes exhibit differences in signal transduction, tissue localization, and regulation of expression. This molecular and biochemical heterogeneity of PGE receptors leads to PGE(2) being the most versatile prostanoid. Studies on knock-out mice deficient in each EP subtype have defined PGE(2) actions mediated by each subtype and identified the role each EP subtype plays in various physiological and pathophysiological responses. Here we review recent advances in PGE receptor research. 相似文献
103.
Alpha-actinin-4 is required for normal podocyte adhesion 总被引:5,自引:0,他引:5
Dandapani SV Sugimoto H Matthews BD Kolb RJ Sinha S Gerszten RE Zhou J Ingber DE Kalluri R Pollak MR 《The Journal of biological chemistry》2007,282(1):467-477
Mutations in the alpha-actinin-4 gene ACTN4 cause an autosomal dominant human kidney disease. Mice deficient in alpha-actinin-4 develop a recessive phenotype characterized by kidney failure, proteinuria, glomerulosclerosis, and retraction of glomerular podocyte foot processes. However, the mechanism by which alpha-actinin-4 deficiency leads to glomerular disease has not been defined. Here, we examined the effect of alpha-actinin-4 deficiency on the adhesive properties of podocytes in vivo and in a cell culture system. In alpha-actinin-4-deficient mice, we observed a decrease in the number of podocytes per glomerulus compared with wild-type mice as well as the presence of podocyte markers in the urine. Podocyte cell lines generated from alpha-actinin-4-deficient mice were less adherent than wild-type cells to glomerular basement membrane (GBM) components collagen IV and laminin 10 and 11. We also observed markedly reduced adhesion of alpha-actinin-4-deficient podocytes under increasing shear stresses. This adhesion deficit was restored by transfecting cells with alpha-actinin-4-GFP. We tested the strength of the integrin receptor-mediated linkages to the cytoskeleton by applying force to microbeads bound to integrin using magnetic pulling cytometry. Beads bound to alpha-actinin-4-deficient podocytes showed greater displacement in response to an applied force than those bound to wild-type cells. Consistent with integrin-dependent alpha-actinin-4-mediated adhesion, phosphorylation of beta1-integrins on alpha-actinin-4-deficient podocytes is reduced. We rescued the phosphorylation deficit by transfecting alpha-actinin-4 into alpha-actinin-4-deficient podocytes. These results suggest that alpha-actinin-4 interacts with integrins and strengthens the podocyte-GBM interaction thereby stabilizing glomerular architecture and preventing disease. 相似文献
104.
Yuna Sugimoto Michiko Murohashi Satoko Arakawa Shinya Honda Shigeomi Shimizu 《Biochemical and biophysical research communications》2019,508(2):480-486
In chemical biology, the elucidation of chemical target is crucial for successful drug development. Because MHC class I molecules present peptides from intracellular damaged proteins, it might be possible to identify targets of a chemical by analyzing peptide sequences on MHC class I. Therefore, we treated cells with the autophagy-inducing chemical TMD-457 and identified the peptides presented on MHC class I. Many of the peptides were derived from molecules involved in ER trafficking and ER stress, which were confirmed by morphological and biochemical analyses. Therefore, our results demonstrate that analyzing MHC class I peptides is useful for the detection of chemical targets. 相似文献
105.
Sakamoto Kazunori Ogiwara Natsuko Kaji Tomomitsu Sugimoto Yurie Ueno Mitsuru Sonoda Masatoshi Matsui Akihiro Ishida Junko Tanaka Maho Totoki Yasushi Shinozaki Kazuo Seki Motoaki 《Journal of plant research》2019,132(4):541-568
Journal of Plant Research - Soybean (Glycine max) roots establish associations with nodule-inducing rhizobia and arbuscular mycorrhizal (AM) fungi. Both rhizobia and AM fungi have been shown to... 相似文献
106.
Adrienne H K Roeder Marisa S Otegui Ram Dixit Charles T Anderson Christine Faulkner Yan Zhang Maria J Harrison Charlotte Kirchhelle Gohta Goshima Jeremy E Coate Jeff J Doyle Olivier Hamant Keiko Sugimoto Liam Dolan Heather Meyer David W Ehrhardt Arezki Boudaoud Carlos Messina 《The Plant cell》2022,34(1):72
As scientists, we are at least as excited about the open questions—the things we do not know—as the discoveries. Here, we asked 15 experts to describe the most compelling open questions in plant cell biology. These are their questions: How are organelle identity, domains, and boundaries maintained under the continuous flux of vesicle trafficking and membrane remodeling? Is the plant cortical microtubule cytoskeleton a mechanosensory apparatus? How are the cellular pathways of cell wall synthesis, assembly, modification, and integrity sensing linked in plants? Why do plasmodesmata open and close? Is there retrograde signaling from vacuoles to the nucleus? How do root cells accommodate fungal endosymbionts? What is the role of cell edges in plant morphogenesis? How is the cell division site determined? What are the emergent effects of polyploidy on the biology of the cell, and how are any such “rules” conditioned by cell type? Can mechanical forces trigger new cell fates in plants? How does a single differentiated somatic cell reprogram and gain pluripotency? How does polarity develop de-novo in isolated plant cells? What is the spectrum of cellular functions for membraneless organelles and intrinsically disordered proteins? How do plants deal with internal noise? How does order emerge in cells and propagate to organs and organisms from complex dynamical processes? We hope you find the discussions of these questions thought provoking and inspiring.We asked 15 experts to address what they consider to be the most compelling open questions in plant cell biology and these are their questions. 相似文献
107.
To identify genes involved in programmed cell death (PCD) in Caenorhabditis elegans, we screened a comprehensive set of chromosomal deficiencies for alterations in the pattern of PCD throughout embryonic development. From a set of 58 deficiencies, which collectively remove approximately 74% of the genome, four distinct classes were identified. In class I (20 deficiencies), no significant deviation from wild type in the temporal pattern of cell corpses was observed, indicating that much of the genome does not contain zygotic genes that perform conspicuous roles in embryonic PCD. The class II deficiencies (16 deficiencies defining at least 11 distinct genomic regions) led to no or fewer-than-normal cell corpses. Some of these cause premature cell division arrest, probably explaining the diminution in cell corpse number; however, others have little effect on cell proliferation, indicating that the reduced cell corpse number is not a direct result of premature embryonic arrest. In class III (18 deficiencies defining at least 16 unique regions), an excess of cell corpses was observed. The developmental stage at which the extra corpses were observed varied among the class III deficiencies, suggesting the existence of genes that perform temporal-specific functions in PCD. The four deficiencies in class IV (defining at least three unique regions), showed unusually large corpses that were, in some cases, attributable to extremely premature arrest in cell division without a concomitant block in PCD. Deficiencies in this last class suggest that the cell death program does not require normal embryonic cell proliferation to be activated and suggest that while some genes required for cell division might also be required for cell death, others are not. Most of the regions identified by these deficiencies do not contain previously identified zygotic cell death genes. There are, therefore, a substantial number of as yet unidentified genes required for normal PCD in C. elegans. 相似文献
108.
Yamauchi Y Ejiri Y Sugimoto T Sueyoshi K Oji Y Tanaka K 《Journal of biochemistry》2001,130(2):257-261
We purified a glutamyl endopeptidase that is a major foliar endopeptidase in cucumber. The endopeptidase had a molecular mass of 400 kDa, consisted of four subunits of 97 kDa, and was inactivated by SH-modifying reagents. Its optimum pH and optimum temperature were 8.0 and 30-37 degrees C, respectively. An internal amino acid sequence of the endopeptidase was highly homologous to a partial sequence of unidentified proteins deduced from genetic information for Arabidopsis thaliana, soybean and rice, but not to the sequences of bacterial glutamyl endopeptidases or animal proteases. Therefore, the unidentified proteins might be glutamyl endopeptidases and be widely distributed only among plant species. The activity of the cucumber glutamyl endopeptidase was inhibited by at least three inhibitors existing in cucumber leaves. One of the inhibitors was a competitive inhibitor of 25 kDa, which did not significantly inhibit commercial endopeptidases derived from animals and microorganisms. This suggests that the cucumber glutamyl endopeptidase might be controlled by endogenous inhibitors in vivo. 相似文献
109.
110.
The thermodynamic parameters of an antiparallel G-quartet formation of d(G4T4G4) with 1 mM divalent cation (Mg(2+), Ca(2+), Mn(2+), Co(2+), and Zn(2+)) were obtained. The thermodynamic parameters showed that the divalent cation destabilizes the antiparallel G-quartet of d(G4T4G4) in the following order: Zn(2+)>Co(2+)>Mn(2+)>Mg(2+)>Ca(2+). In addition, a higher concentration of a divalent cation induced a transition from an antiparallel to a parallel G-quartet structure. These results indicate that these divalent cations are a good tool for regulating the G-quartet structures. 相似文献