全文获取类型
收费全文 | 419篇 |
免费 | 34篇 |
出版年
2022年 | 4篇 |
2021年 | 5篇 |
2020年 | 8篇 |
2019年 | 4篇 |
2018年 | 12篇 |
2017年 | 5篇 |
2016年 | 11篇 |
2015年 | 24篇 |
2014年 | 20篇 |
2013年 | 32篇 |
2012年 | 31篇 |
2011年 | 31篇 |
2010年 | 24篇 |
2009年 | 17篇 |
2008年 | 26篇 |
2007年 | 24篇 |
2006年 | 22篇 |
2005年 | 29篇 |
2004年 | 19篇 |
2003年 | 19篇 |
2002年 | 22篇 |
2001年 | 7篇 |
2000年 | 3篇 |
1999年 | 4篇 |
1998年 | 5篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1993年 | 4篇 |
1992年 | 2篇 |
1991年 | 4篇 |
1990年 | 5篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 3篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有453条查询结果,搜索用时 171 毫秒
381.
The Hsp60 protein of Helicobacter pylori: structure and immune response in patients with gastroduodenal diseases 总被引:17,自引:2,他引:15
Giovanni Macchia Annalisa Massone Daniela Burroni Antonello Covacci Stefano Censini Rino Rappuoli 《Molecular microbiology》1993,9(3):645-652
Helicobacter pylori is a human pathogen that has been associated with gastritis, peptic ulcer and gastric carcinoma. The role of the direct action of H. pylori virulence factors and of the induction of autoreactive immunity in the development of chronic gastritis has not been clarified yet. Here we report the cloning and molecular characterization of a gene of H. pylori coding for a protein of 58kDa, recognized by sera of patients affected by H. pylori-induced gastroduodenal diseases. This antigen is present in all the H. pylori strains tested and it belongs to the Hsp60 family of heat-shock proteins, with high homology with other bacterial and eukaryotic proteins of the same family. This class of homologous proteins has been implicated in the induction of autoimmune disorders in different systems. The presence in infected patients of anti-H. pylori Hsp60 antibodies, potentially cross-reacting with the human homologue, and cross-reactivity between human Hsp60 and a rabbit antiserum against H. pylori Hsp60 suggest that a role of this protein in gastroduodenal diseases is possible. 相似文献
382.
Valentina Quaresima Cinzia L. Ursini Giancaterino Gualtieri Antonello Sotgiu Marco Ferrari 《生物化学与生物物理学报:疾病的分子基础》1993,1182(1):115-118
The effects of fraction of inspired oxygen (FiO2) on the reduction of a nitroxide free radical were studied by X-band electron paramagnetic resonance (EPR) monitoring of circulating rat blood. The decay half-life of the metabolism/elimination phase increased significantly by 24 ± 8% during hyperoxia and decreased significantly by 16 ± 4% during hypoxia. 相似文献
383.
Genetic analysis of muscle specification, formation and function in model systems has provided valuable insight into human muscle physiology and disease. Studies in Drosophila have been particularly useful for discovering key genes involved in muscle specification, myoblast fusion, and sarcomere organization. The muscles of the Drosophila female reproductive system have received little attention despite extensive work on oogenesis. We have used newly available GFP protein trap lines to characterize of ovarian muscle morphology and sarcomere organization. The muscle cells surrounding the oviducts are multinuclear with highly organized sarcomeres typical of somatic muscles. In contrast, the two muscle layers of the ovary, which are derived from gonadal mesoderm, have a mesh-like morphology similar to gut visceral muscle. Protein traps in the Fasciclin 3 gene produced Fas3::GFP that localized in dots around the periphery of epithelial sheath cells, the muscle surrounding ovarioles. Surprisingly, the epithelial sheath cells each contain a single nucleus, indicating these cells do not undergo myoblast fusion during development. Consistent with this observation, we were able to use the Flp/FRT system to efficiently generate genetic mosaics in the epithelial sheath, suggesting these cells provide a new opportunity for clonal analysis of adult striated muscle. 相似文献
384.
385.
386.
Francesco Fiorentino Marta De Angelis Martina Menna Annarita Rovere Anna Maria Caccuri Francesca DAcunzo Anna Teresa Palamara Lucia Nencioni Dante Rotili Antonello Mai 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):2128
Influenza viruses represent a major threat to human health and are responsible for seasonal epidemics, along with pandemics. Currently, few therapeutic options are available, with most drugs being at risk of the insurgence of resistant strains. Hence, novel approaches targeting less explored pathways are urgently needed. In this work, we assayed a library of nitrobenzoxadiazole derivatives against the influenza virus A/Puerto Rico/8/34 H1N1 (PR8) strain. We identified three promising 4-thioether substituted nitrobenzoxadiazoles (12, 17, and 25) that were able to inhibit viral replication at low micromolar concentrations in two different infected cell lines using a haemagglutination assay. We further assessed these molecules using an In-Cell Western assay, which confirmed their potency in the low micromolar range. Among the three molecules, 12 and 25 displayed the most favourable profile of activity and selectivity and were selected as hit compounds for future optimisation studies. 相似文献
387.
388.
Mazzarella L Vergara A Vitagliano L Merlino A Bonomi G Scala S Verde C di Prisco G 《Proteins》2006,65(2):490-498
The Root effect is a widespread property in fish hemoglobins (Hbs) that produces a drastic reduction of cooperativity and oxygen-binding ability at acidic pH. Here, we report the high-resolution structure of the deoxy form of Hb isolated from the Antarctic fish Trematomus bernacchii (HbTb) crystallized at pH 6.2 and 8.4. The structure at acidic pH has been previously determined at a moderate resolution (Ito et al., J Mol Biol 1995;250:648-658). Our results provide a clear picture of the events occurring upon the pH increase from 6.2 to 8.4, observed within a practically unchanged crystal environment. In particular, at pH 8.4, the interaspartic hydrogen bond at the alpha(1)beta(2) interface is partially broken, suggesting a pK(a) close to 8.4 for Asp95alpha. In addition, a detailed survey of the histidine modifications, caused by the change in pH, also indicates that at least three hot regions of the molecule are modified (Ebeta helix, Cbeta-tail, CDalpha corner) and can be considered to be involved at various levels in the release of the Root protons. Most importantly, at the CDalpha corner, the break of the salt bridge Asp48alpha-His55alpha allows us to describe a detailed mechanism that transmits the modification from the CDalpha corner far to the alpha heme. More generally, the results shed light on the role played by the histidine residues in modulating the strength of the Root effect and also support the emerging idea that the structural determinants, at least for a part of the Root effect, are specific of each Hb endowed with this property. 相似文献
389.
Scippa GS Di Michele M Di Iorio A Costa A Lasserre B Chiatante D 《Annals of botany》2006,97(5):857-866
BACKGROUND AND AIMS: Plant anchorage is governed by complex, finely regulated mechanisms that occur at a morphological, architectural and anatomical level. Spanish broom (Spartium junceum) is a woody plant frequently found on slopes--a condition that affects plant anchorage. This plant grows throughout the Mediterranean area where it plays an important role in preventing landslides. Spanish broom seedlings respond promptly to slope by altering stem and root morphology. The aim of this study was to investigate the mechanisms whereby the root system of Spanish broom seedlings adapts to ensure anchorage to the ground. METHODS: Seedlings were grown in tilted and untilted pots under controlled conditions. The root apparatus was removed at different times of growth and subjected to morphological, biomechanical and molecular analyses. KEY RESULTS: In slope-grown seedlings, changes in root system morphology, pulling strength and chemical lignin content, all features related to plant anchorage in the soil, were related to seedling age. cDNA-AFLP analysis revealed changes in the expression of several genes in root systems of slope-grown plants. BLAST analysis showed that some differentially expressed genes are homologues of genes induced by environmental stresses in other plant species, and/or are involved in the production of strengthening materials. CONCLUSION: Plants use various mechanisms/strategies to respond to slope depending on their developmental stage. 相似文献
390.
Komazin-Meredith G Petrella RJ Santos WL Filman DJ Hogle JM Verdine GL Karplus M Coen DM 《Structure (London, England : 1993)》2008,16(8):1214-1225
Processivity factors tether the catalytic subunits of DNA polymerases to DNA so that continuous synthesis of long DNA strands is possible. The human cytomegalovirus DNA polymerase subunit UL44 forms a C clamp-shaped dimer intermediate in structure between monomeric herpes simplex virus UL42, which binds DNA directly via a basic surface, and the trimeric sliding clamp PCNA, which encircles DNA. To investigate how UL44 interacts with DNA, calculations were performed in which a 12 bp DNA oligonucleotide was docked to UL44. The calculations suggested that UL44 encircles DNA, which interacts with basic residues both within the cavity of the C clamp and in flexible loops of UL44 that complete the "circle." The results of mutational and crosslinking studies were consistent with this model. Thus, UL44 is a "hybrid" of UL42 and PCNA: its structure is intermediate between the two and its mode of interaction with DNA has elements of both. 相似文献