全文获取类型
收费全文 | 1022篇 |
免费 | 79篇 |
出版年
2023年 | 10篇 |
2022年 | 9篇 |
2021年 | 28篇 |
2020年 | 22篇 |
2019年 | 31篇 |
2018年 | 38篇 |
2017年 | 23篇 |
2016年 | 36篇 |
2015年 | 58篇 |
2014年 | 62篇 |
2013年 | 70篇 |
2012年 | 71篇 |
2011年 | 66篇 |
2010年 | 39篇 |
2009年 | 52篇 |
2008年 | 49篇 |
2007年 | 55篇 |
2006年 | 65篇 |
2005年 | 60篇 |
2004年 | 49篇 |
2003年 | 44篇 |
2002年 | 20篇 |
2001年 | 13篇 |
2000年 | 11篇 |
1999年 | 9篇 |
1998年 | 8篇 |
1997年 | 7篇 |
1996年 | 10篇 |
1995年 | 5篇 |
1994年 | 7篇 |
1993年 | 7篇 |
1992年 | 7篇 |
1991年 | 8篇 |
1990年 | 8篇 |
1989年 | 4篇 |
1988年 | 6篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1981年 | 4篇 |
1980年 | 2篇 |
1978年 | 3篇 |
1968年 | 1篇 |
1966年 | 1篇 |
1961年 | 1篇 |
1960年 | 1篇 |
1955年 | 1篇 |
1954年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有1101条查询结果,搜索用时 15 毫秒
41.
Delia Gagliardi Giacomo P. Comi Nereo Bresolin Stefania Corti 《Journal of cellular and molecular medicine》2019,23(3):1647-1656
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting upper and lower motor neurons (MNs), resulting in paralysis and precocious death from respiratory failure. Although the causes of ALS are incompletely understood, the role of alterations in RNA metabolism seems central. MicroRNAs (miRNAs) are noncoding RNAs implicated in the regulation of gene expression of many relevant physiological processes, including cell death. The recent model of programmed cell death (PCD) encompasses different mechanisms, from apoptosis to regulated necrosis (RN), in particular necroptosis. Both apoptosis and necroptosis play a significant role in the progressive death of MNs in ALS. In this review, we present key research related to miRNAs that modulate apoptosis and RN pathways in ALS. We also discuss whether these miRNAs represent potential targets for therapeutic development in patients. 相似文献
42.
Soru Santina Malavasi Veronica Caboni Pierluigi Concas Alessandro Cao Giacomo 《Extremophiles : life under extreme conditions》2019,23(1):79-89
Extremophiles - The extremophile green alga Coccomyxa melkonianii SCCA 048 was investigated to evaluate its ability to grow in culture media with different pH. Specifically, Coccomyxa melkonianii... 相似文献
43.
Gustavo Benevides Martins Giacomo Giacomelli Oliver Goldbeck Gerd M. Seibold Marc Bramkamp 《Molecular microbiology》2019,111(5):1335-1354
Many bacteria take up carbohydrates by membrane‐integral sugar specific phosphoenolpyruvate‐dependent carbohydrate:phosphotransferase systems (PTS). Although the PTS is centrally involved in regulation of carbon metabolism in different bacteria, little is known about localization and putative oligomerization of the permease subunits (EII). Here, we analyzed localization of the fructose specific PtsF and the glucose specific PtsG transporters, as well as the general components EI and HPr from Corynebacterium glutamicum using widefield and single molecule localization microscopy. PtsF and PtsG form membrane embedded clusters that localize in a punctate pattern. Size, number and fluorescence of the membrane clusters change upon presence or absence of the transported substrate, and a direct influence of EI and HPr was not observed. In presence of the transport substrate, EII clusters significantly increased in size. Photo‐activated localization microscopy data revealed that, in presence of different carbon sources, the number of EII proteins per cluster remains the same, however, the density of these clusters reduces. Our work reveals a simple mechanism for efficient membrane occupancy regulation. Clusters of PTS EII transporters are densely packed in absence of a suitable substrate. In presence of a transported substrate, the EII proteins in individual clusters occupy larger membrane areas. 相似文献
44.
45.
Cecilia Soldatini Yuri V. Albores-Barajas Alejandro Ramos-Rodriguez Adrian Munguia-Vega Eduardo González-Rodríguez Carlo Catoni Giacomo Dell'Omo 《Population Ecology》2019,61(2):227-239
During the breeding season, seabird foraging trips are constrained by nest attendance schedule and are necessarily colony centred. Oceanographic cues play a major role in the choice of foraging areas to minimize the time spent away from the nest. Here, we analysed the foraging tracks of Black-vented Shearwaters Puffinus opisthomelas during the incubation and chick-rearing periods of 2016 and 2017 at Isla Natividad (Mexico). We applied expectation-maximization binary clustering to track data to clusterize different behaviour patterns during foraging flights. We then applied binary generalized linear mixed models to characterize of foraging areas based on of environmental variables. We finally used kernel estimation techniques to describe main foraging areas. In 2016, breeding shearwaters used two core areas for foraging and resting on the water; the core area delineated by males was located northward from the colony in the Vizcaino Bay and the core area for females was located southward from the colony at the entrance of San Ignacio Lagoon. In 2017, males and females used the same areas with no evident segregation. Our study provided the first information on Black-vented Shearwater foraging areas during the breeding season and indicated that sexual segregation within coastal waters off the central Baja California Peninsula might be a foraging strategy during years of warmer ocean, likely less productive regimes. Factors including ocean-climate-mediated sexual segregation at sea, leading to interannual variation in foraging areas, should be considered when evaluating management actions intended to protect critical foraging habitats for Black-vented Shearwaters. 相似文献
46.
Lipase from Burkholderia cepacia (lipase BC) and lipase B from Candida antarctica (CALB) show an increase of the transesterification activity in toluene (up to 2.4- and 1.7-fold, respectively), when lyophilized with 18-crown-6. Nevertheless, the increase was observed only for low (less than 100) 18-crown-6/lipase molar ratio, while at higher ratios, the activity decreased for both enzymes to values lower than those obtained in the absence of the additive. In 1,4-dioxane, the activation is lower for lipase BC (1.7-fold) and for CALB (1.5-fold). Concerning enantioselectivity, tested in the kinetic resolution of 6-methyl-5-hepten-2-ol, only in the case of CALB, an effect of the additive (the E value varied from about 120 to 280) was observed. In water, 4% (w/w) of 18-crown-6 caused a loss of activity in the hydrolysis of p-nitrophenyl laurate of about 88 and 99.75%, compared to that observed in the absence of the crown ether for CALB and lipase BC, respectively. These data and the conformational analysis of both lipases, carried out by FT/IR spectroscopy indicate that the enzyme inactivation in water and in organic solvents at 18-crown-6/lipase molar ratios, higher than 100 might be due to conformational changes caused by the additive. Instead, at molar ratios lower than 100, 18-crown-6 might increase the activity - particularly, in toluene - thanks to the fact that in its presence, the enzyme has an hydrogen bonds pattern, more similar to that in water. This suggests that the additive would be able to provide the enzyme with more water. 相似文献
47.
Is there an objective, biological basis for the experience of beauty in art? Or is aesthetic experience entirely subjective? Using fMRI technique, we addressed this question by presenting viewers, naïve to art criticism, with images of masterpieces of Classical and Renaissance sculpture. Employing proportion as the independent variable, we produced two sets of stimuli: one composed of images of original sculptures; the other of a modified version of the same images. The stimuli were presented in three conditions: observation, aesthetic judgment, and proportion judgment. In the observation condition, the viewers were required to observe the images with the same mind-set as if they were in a museum. In the other two conditions they were required to give an aesthetic or proportion judgment on the same images. Two types of analyses were carried out: one which contrasted brain response to the canonical and the modified sculptures, and one which contrasted beautiful vs. ugly sculptures as judged by each volunteer. The most striking result was that the observation of original sculptures, relative to the modified ones, produced activation of the right insula as well as of some lateral and medial cortical areas (lateral occipital gyrus, precuneus and prefrontal areas). The activation of the insula was particularly strong during the observation condition. Most interestingly, when volunteers were required to give an overt aesthetic judgment, the images judged as beautiful selectively activated the right amygdala, relative to those judged as ugly. We conclude that, in observers naïve to art criticism, the sense of beauty is mediated by two non-mutually exclusive processes: one based on a joint activation of sets of cortical neurons, triggered by parameters intrinsic to the stimuli, and the insula (objective beauty); the other based on the activation of the amygdala, driven by one''s own emotional experiences (subjective beauty). 相似文献
48.
Giobbe S Marceddu S Scherm B Zara G Mazzarello VL Budroni M Migheli Q 《FEMS yeast research》2007,7(8):1389-1398
A biofilm-forming strain of Pichia fermentans proved to be most effective in controlling brown rot on apple fruit when coinoculated into artificial wounds with a phytopathogenic isolate of Monilinia fructicola. Culture filtrates and autoclaved cells had no significant influence on the disease. When sprayed onto the apple fruit surface, this yeast formed a thin biofilm but failed to colonize the underlying tissues. When inoculated into wounds artificially inflicted to peach fruit or when sprayed onto the surface of peach fruit, the same strain showed an unexpected pathogenic behaviour, causing rapid decay of fruit tissues even in the absence of M. fructicola. Both optical and scanning electron microscopy were used to evaluate the pattern of fruit tissue colonization by P. fermentans. While on apple surface and within the apple wound the antagonist retained its yeast-like shape, colonization of peach fruit tissue was always characterized by a transition from budding growth to pseudohyphal growth. These results suggest that pseudohyphal growth plays a major role in governing the potential pathogenicity of P. fermentans, further emphasizing the importance of a thorough risk assessment for the safe use of any novel biocontrol agent. 相似文献
49.
Comparative proteome profiling and functional analysis of chronic myelogenous leukemia cell lines 总被引:1,自引:0,他引:1
Fontana S Alessandro R Barranca M Giordano M Corrado C Zanella-Cleon I Becchi M Kohn EC De Leo G 《Journal of proteome research》2007,6(11):4330-4342
The aim of the present study was the molecular profiling of different Ph+ chronic myelogenous leukemia (CML) cell lines (LAMA84, K562, and KCL22) by a proteomic approach. By employing two-dimensional gel electrophoresis combined with mass spectrometry analysis, we have identified 191 protein spots corresponding to 142 different proteins. Among these, 63% were cancer-related proteins and 74% were described for the first time in leukemia cells. Multivariate analysis highlighted significant differences in the global proteomic profile of the three CML cell lines. In particular, the detailed analysis of 35 differentially expressed proteins revealed that LAMA84 cells preferentially expressed proteins associated with an invasive behavior, while K562 and KCL22 cells preferentially expressed proteins involved in drug resistance. These data demonstrate that these CML cell lines, although representing the same pathological phenotype, show characteristics in their protein expression profile that suggest different phenotypic leukemia subclasses. These data contribute a new potential characterization of the CML phenotype and may help to understand interpatient variability in the progression of disease and in the efficacy of a treatment. 相似文献
50.
Giacomo Pozzoli Hany E. Marei Asma Althani Alma Boninsegna Patrizia Casalbore Lionel N. J. L. Marlier Giulia Lanzilli Manuela Zonfrillo Giovanna Petrucci Bianca Rocca Pierluigi Navarra Alessandro Sgambato Carlo Cenciarelli 《Journal of cellular physiology》2019,234(9):15459-15471
Several clinical studies indicated that the daily use of aspirin or acetylsalicylic acid reduces the cancer risk via cyclooxygenases (Cox-1 and Cox-2) inhibition. In addition, aspirin-induced Cox-dependent and -independent antitumor effects have also been described. Here we report, for the first time, that aspirin treatment of human glioblastoma cancer (GBM) stem cells, a small population responsible for tumor progression and recurrence, is associated with reduced cell proliferation and motility. Aspirin did not interfere with cell viability but induced cell-cycle arrest. Exogenous prostaglandin E2 significantly increased cell proliferation but did not abrogate the aspirin-mediated growth inhibition, suggesting a Cox-independent mechanism. These effects appear to be mediated by the increase of p21 waf1 and p27 Kip1, associated with a reduction of Cyclin D1 and Rb1 protein phosphorylation, and involve the downregulation of key molecules responsible for tumor development, that is, Notch1, Sox2, Stat3, and Survivin. Our results support a possible role of aspirin as adjunctive therapy in the clinical management of GBM patients. 相似文献