全文获取类型
收费全文 | 263篇 |
免费 | 18篇 |
出版年
2021年 | 7篇 |
2020年 | 6篇 |
2019年 | 11篇 |
2018年 | 8篇 |
2017年 | 9篇 |
2016年 | 14篇 |
2015年 | 13篇 |
2014年 | 10篇 |
2013年 | 9篇 |
2012年 | 15篇 |
2011年 | 14篇 |
2010年 | 12篇 |
2009年 | 7篇 |
2008年 | 8篇 |
2007年 | 10篇 |
2006年 | 12篇 |
2005年 | 10篇 |
2004年 | 5篇 |
2003年 | 8篇 |
2002年 | 10篇 |
2001年 | 8篇 |
2000年 | 7篇 |
1999年 | 6篇 |
1998年 | 7篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 5篇 |
1988年 | 2篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1975年 | 2篇 |
1973年 | 1篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1970年 | 1篇 |
1969年 | 3篇 |
1968年 | 1篇 |
1967年 | 2篇 |
1966年 | 1篇 |
排序方式: 共有281条查询结果,搜索用时 15 毫秒
81.
82.
Elena Odintsova Guillaume van Niel Hélène Conjeaud Gra?a Raposo Ryo Iwamoto Eisuke Mekada Fedor Berditchevski 《The Journal of biological chemistry》2013,288(36):26323-26334
Ligand-induced ubiquitylation of EGF receptor (EGFR) is an important regulatory mechanism that controls endocytic trafficking of the receptor and its signaling potential. Here we report that tetraspanin CD82/KAI1 specifically suppresses ubiquitylation of EGFR after stimulation with heparin-binding EGF or amphiregulin and alters the rate of recruitment of the activated receptor to EEA1-positive endosomes. The suppressive effect of CD82 is dependent on the heparin-binding domain of the ligand. Deletion of the C-terminal cytoplasmic domain of CD82 (CD82ΔC mutant) inhibits endocytic trafficking of the tetraspanin and compromises its activity toward heparin-binding EGF-activated EGFR. Reduced ubiquitylation of EGFR is accompanied by PKC-dependent increase in serine phosphorylation of c-Cbl in cells expressing elevated levels of CD82. Furthermore, phosphorylation of threonine 654 (PKC phosphorylation site) in the juxtamembrane domain of the receptor is considerably increased in CD82-expressing cells. These results describe previously unsuspected links between tetraspanin proteins and ubiquitylation of their molecular partners (e.g., EGFR). Our data identify CD82 as a new regulator of c-Cbl, which discriminatively controls the activity of this E3 ubiquitin ligase toward heparin-binding ligand-EGFR pairs. Taken together, these observations provide an important new insight into the modulatory role of CD82 in endocytic trafficking of EGF receptor. 相似文献
83.
Weifeng Xu MS Xinwei Chen MD Yexin Wang MS Baoting Fan MS Ke Guo MS Chi Yang MD Shiqi Yu MD Yichuan Pang MD Shanyong Zhang MD 《Journal of cellular physiology》2020,235(3):3022-3032
Considering the high rate of osteoclast-related diseases worldwide, research targeting osteoclast formation/function is crucial. In vitro, we demonstrated that chitooligosaccharide (CS) dramatically inhibited osteoclastogenesis as well as osteoclast function dose-dependently. CS suppressed osteoclast-specific genes expression during osteoclastogenesis. Furthermore, we found that CS attenuated receptor activator of nuclear factor kappa B ligand (RANKL)-mediated mitogen-activated protein kinase (MAPK) pathway involving p38, erk1/2, and jnk, leading to the reduced expression of c-fos and nuclear factor of activated T cells c1 (NFATc1) during osteoclast differentiation. In vivo, we found CS protected rats from periodontitis-induced alveolar bone loss by micro-computerized tomography and histological analysis. Overall, CS inhibited RANKL-induced osteoclastogenesis and ligature-induced rat periodontitis model, probably by suppressing the MAPK/c-fos/NFATc1 signaling pathway. Therefore, CS may be a safe and promising treatment for osteoclast-related diseases. 相似文献
84.
85.
The development of contractile apparatus was subjected to comparative analysis during ontogenesis of the mussel Mytilus trossulus. Indirect immunofluorescence with the polyclonal antibody against mussel twitchin, a protein of thick filaments, and florescent phalloidin as a marker of filamentous cell actin were used to monitor changes in the developing muscle system at different larval stages. The first definitive muscle structures were found at the late trochophore stage (36 h after fertilization) and starting from the midveliger stage (96 h), striated muscles, which are never present in adult mussels, were distinctly seen. The striated muscle periodicity was 1.25 microm in both mussle larvae and adult scallop. The contractile activities of veliger and adult muscles were measured using an electronic signal-processing videosystem. This work is the first complex study of morphological, biochemical, and physiological characteristics of the muscle system in the larvae and adult mollusks. 相似文献
86.
87.
Antonina A. Berkut Dinara R. Usmanova Steve Peigneur Peter B. Oparin Konstantin S. Mineev Tatyana I. Odintsova Jan Tytgat Alexander S. Arseniev Eugene V. Grishin Alexander A. Vassilevski 《The Journal of biological chemistry》2014,289(20):14331-14340
In this study, we present the spatial structure of the wheat antimicrobial peptide (AMP) Tk-AMP-X2 studied using NMR spectroscopy. This peptide was found to adopt a disulfide-stabilized α-helical hairpin fold and therefore belongs to the α-hairpinin family of plant defense peptides. Based on Tk-AMP-X2 structural similarity to cone snail and scorpion potassium channel blockers, a mutant molecule, Tk-hefu, was engineered by incorporating the functionally important residues from κ-hefutoxin 1 onto the Tk-AMP-X2 scaffold. The designed peptide contained the so-called essential dyad of amino acid residues significant for channel-blocking activity. Electrophysiological studies showed that although the parent peptide Tk-AMP-X2 did not present any activity against potassium channels, Tk-hefu blocked Kv1.3 channels with similar potency (IC50 ∼ 35 μm) to κ-hefutoxin 1 (IC50 ∼ 40 μm). We conclude that α-hairpinins are attractive in their simplicity as structural templates, which may be used for functional engineering and drug design. 相似文献
88.
Andrey V. Boroda Nina A. Aizdaicher Nelly A. Odintsova 《Journal of applied phycology》2014,26(1):387-397
The development of cryopreservation methods for microalgae opens great prospects for marine biotechnology and aims to establish a bank of cryopreserved cultures. Eight of ten marine microalgae species used in this study (the diatoms, green, red, and golden algae), including five previously untested species, were successfully recovered after freezing to ultra-low temperatures (?196 °C) using penetrating (dimethyl sulfoxide, glycerol, and ethylene glycol) and non-penetrating (trehalose and polyvinylpyrrolidone) cryoprotectants. We found that ethylene glycol in combination with trehalose possessed the most effective cryoprotective activity among the algae cryoprotectants tested. However, the chief factor for the successful preservation of microalgal cells during freeze–thawing was shown to be the cooling rate. Cooling was performed in two ways: step or fast droplet freezing. The droplet freezing described here was effective only for cryopreserving green algae, whereas step freezing was optimal for all other algal species. Three diatoms of the genus Attheya were successfully cryopreserved for the first time, but none of the tested protocols had a positive result for the diatoms belonging to Pseudo-nitzschia. The failure may be explained rather by peculiarities in the cell wall composition (higher content of silica and fewer organic components) than by the specific (long and thin) shape of these cells. The pigment content in all of the studied species tended to decrease after thawing as compared with unfrozen cells and increase significantly during cell recovery. Cryosensitivity of marine algae depended on the differences in natural intrinsic characteristics rather than their taxonomic position. 相似文献
89.
90.
Elina MS Paaso Maritta S Jaakkola Aino K Rantala Timo T Hugg Jouni JK Jaakkola 《Respiratory research》2014,15(1)
BackgroundFamily history of asthma and other allergic diseases have been linked to the risk of childhood asthma previously, but little is known about their effect on the age-of-onset and persistency of asthma until young adulthood.MethodsWe assessed the effect of the family history of asthma and allergic diseases on persistent vs. transient, and early- vs. late-onset persistent asthma in The Espoo Cohort Study 1991–2011, a population-based cohort study of 1623 subjects (follow-up rate 63.2%). The determinants were any family history (any parent or sibling); maternal; paternal; siblings only; parents only; and both siblings and parents. Analyses were conducted separately for asthma and allergic diseases while taking the other disease into account as a confounding factor. The outcomes were persistent, transient, early-onset persistent (<13 years) and late-onset persistent asthma. Adjusted risk ratios (RR) were calculated applying Poisson regression. Q-statistics were used to assess heterogeneity between RRs.ResultsFamily history was associated with the different subtypes but the magnitude of effect varied quantitatively. Any family history of asthma was a stronger determinant of persistent (adjusted RR = 2.82, 95% CI 1.99-4.00) than transient asthma (1.65, 1.03-2.65) (heterogeneity: P = 0.07) and on early-onset than late-onset persistent asthma. Also any family history of allergic diseases was a stronger determinant of persistent and early-onset asthma. The impact of paternal asthma continued to young adulthood (early-onset: 3.33, 1.57-7.06 vs. late-onset 2.04, 0.75-5.52) while the influence of maternal asthma decreased with age (Early-onset 3.94, 2.11-7.36 vs. Late-onset 0.88, 0.28-2.81). Paternal allergic diseases did not follow the pattern of paternal asthma, since they showed no association with late-onset asthma. Also the effect estimates for other subtypes were lower than in other hereditary groups (persistent 1.29, 0.75-2.22 vs. transient 1.20, 0.67-2.15 and early-onset 1.86, 0.95-3.64 vs. late-onset 0.64, 0.22-1.80).ConclusionsFamily history of asthma and allergic diseases are strong determinants of asthma, but the magnitude of effect varies according to the hereditary group so that some subtypes have a stronger hereditary component, and others may be more strongly related to environmental exposures. Our results provide useful information for assessing the prognosis of asthma based on a thorough family history. 相似文献