全文获取类型
收费全文 | 992篇 |
免费 | 81篇 |
国内免费 | 1篇 |
出版年
2023年 | 6篇 |
2022年 | 4篇 |
2021年 | 27篇 |
2020年 | 9篇 |
2019年 | 16篇 |
2018年 | 31篇 |
2017年 | 23篇 |
2016年 | 33篇 |
2015年 | 53篇 |
2014年 | 43篇 |
2013年 | 57篇 |
2012年 | 66篇 |
2011年 | 78篇 |
2010年 | 38篇 |
2009年 | 35篇 |
2008年 | 56篇 |
2007年 | 59篇 |
2006年 | 44篇 |
2005年 | 63篇 |
2004年 | 42篇 |
2003年 | 53篇 |
2002年 | 46篇 |
2001年 | 12篇 |
2000年 | 5篇 |
1999年 | 16篇 |
1998年 | 6篇 |
1997年 | 8篇 |
1996年 | 11篇 |
1995年 | 5篇 |
1994年 | 3篇 |
1992年 | 11篇 |
1991年 | 9篇 |
1990年 | 4篇 |
1989年 | 10篇 |
1988年 | 5篇 |
1987年 | 5篇 |
1986年 | 5篇 |
1985年 | 5篇 |
1984年 | 7篇 |
1983年 | 5篇 |
1982年 | 5篇 |
1981年 | 6篇 |
1980年 | 5篇 |
1979年 | 8篇 |
1978年 | 4篇 |
1977年 | 5篇 |
1976年 | 3篇 |
1974年 | 4篇 |
1971年 | 5篇 |
1969年 | 2篇 |
排序方式: 共有1074条查询结果,搜索用时 15 毫秒
31.
Chemical hydrolysis of lignocellulosic biomass (LB) produces a number of inhibitors in addition to sugars. These inhibitors include lignin-derived phenolics, carbohydrate-derived furans, and weak acids that have shown a marked effect on the productivities of various metabolites and the growth of biocatalysts in the fermentative reaction. In the past, a number of physicochemical and biological approaches have been proposed to overcome these fermentation inhibitors, including modified fermentative strategies. Additionally, the timely intervention of genetic engineering has provided an impetus to develop suitable technologies for the detoxification of lignocellulosics in biorefineries. However, the improvements in detoxification strategies for lignocellulose hydrolysates have resulted in significant loss of sugars after detoxification. Hydrolysis of myco-LB (LB after fungal pretreatment) has been recognized as a promising approach to avoid fermentation inhibitors and improve total sugar recovery. Biotechnological inventions have also made it possible to widen the range of suitable biocatalysts for biorefineries by microbial-routed induction of enzymatic expression for the elimination of inhibitors, eventually improving ethanol production from acid hydrolysates. This article aims to highlight the strategies that have been adopted to detoxify lignocellulosic hydrolysates and their effects on the chemical composition of the hydrolysates to improve the fermentability of lignocellulosics. In addition, genetic manipulation could widen the availability and variety of substrates and modify the metabolic routes to produce bioethanol or other value-added compounds in an efficient manner. 相似文献
32.
Silvio a Beccara Tatjana ?krbi? Roberto Covino Cristian Micheletti Pietro Faccioli 《PLoS computational biology》2013,9(3)
We report on atomistic simulation of the folding of a natively-knotted protein, MJ0366, based on a realistic force field. To the best of our knowledge this is the first reported effort where a realistic force field is used to investigate the folding pathways of a protein with complex native topology. By using the dominant-reaction pathway scheme we collected about 30 successful folding trajectories for the 82-amino acid long trefoil-knotted protein. Despite the dissimilarity of their initial unfolded configuration, these trajectories reach the natively-knotted state through a remarkably similar succession of steps. In particular it is found that knotting occurs essentially through a threading mechanism, involving the passage of the C-terminal through an open region created by the formation of the native -sheet at an earlier stage. The dominance of the knotting by threading mechanism is not observed in MJ0366 folding simulations using simplified, native-centric models. This points to a previously underappreciated role of concerted amino acid interactions, including non-native ones, in aiding the appropriate order of contact formation to achieve knotting. 相似文献
33.
Annamaria Spina Luca Sorvillo Francesca Di Maiolo Antonietta Esposito Raffaella D'Auria Davide Di Gesto Emilio Chiosi Silvio Naviglio 《Journal of cellular physiology》2013,228(1):198-206
Osteosarcoma is the most common malignant primary bone tumor in children and adolescents. The clinical outcome for osteosarcoma remains discouraging despite aggressive surgery and intensive radiotherapy and chemotherapy regimens. Thus, novel therapeutic approaches are needed. Previously, we have shown that inorganic phosphate (Pi) inhibits proliferation and aggressiveness of human osteosarcoma U2OS cells identifying adenylate cyclase, beta3 integrin, Rap1, ERK1/2 as proteins whose expression and function are relevantly affected in response to Pi. In this study, we investigated whether Pi could affect chemosensitivity of osteosarcoma cells and the underlying molecular mechanisms. Here, we report that Pi inhibits proliferation of p53‐wild type U2OS cells (and not of p53‐null Saos and p53‐mutant MG63 cells) by slowing‐down cell cycle progression, without apoptosis occurrence. Interestingly, we found that Pi strongly enhances doxorubicin‐induced cytotoxicity in U2OS, and not in Saos and MG63 cells, by apoptosis induction, as revealed by a marked increase of sub‐G1 population, Bcl‐2 downregulation, caspase‐3 activation, and PARP cleavage. Remarkably, Pi/doxorubicin combination‐induced cytotoxicity was accompanied by an increase of p53 protein levels and of p53 target genes mdm2, p21 and Bax, and was significantly reduced by the p53 inhibitor pifithrine‐alpha. Moreover, the doxorubicin‐induced cytotoxicity was associated with ERK1/2 pathway inhibition in response to Pi. Altogether, our data enforce the evidence of Pi as a novel signaling molecule capable of inhibiting ERK pathway and inducing sensitization to doxorubicin of osteosarcoma cells by p53‐dependent apoptosis, implying that targeting Pi levels might represent a rational strategy for improving osteosarcoma therapy. J. Cell. Physiol. 228: 198–206, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
34.
Francesca Ripamonti Luisa Albano Anna Rossini Serena Borrelli Sonia Fabris Roberto Mantovani Antonino Neri Andrea Balsari Alessandra Magnifico Elda Tagliabue 《Journal of cellular physiology》2013,228(4):871-878
Many squamous cell carcinomas (SCCs) are characterized by high levels of EGFR and by overexpression of the ΔNp63α isoform. Here, we investigated the regulation of ΔNp63α expression upon EGFR activation and the role of the EGFR–ΔNp63α axis in proliferation of SCC tumor‐initiating cells (TICs). SCC cell lines A‐431, Cal‐27, and SCC‐25 treated with EGF showed a time‐dependent increase in ΔNp63α expression at the protein and mRNA levels, which was blocked by the tyrosine kinase inhibitor (TKI) Lapatinib. RNA interference experiments suggested the role of STAT3 in regulating ΔNp63α expression downstream of EGFR. Inactivation of EGFR by the monoclonal antibody Cetuximab and RNA interference against STAT3 or ΔNp63α impaired the TICs ability to grow under non‐differentiating conditions. Radiation treatment, which triggers EGFR activation, induced ΔNp63α accumulation without affecting TICs proliferation, whereas the combination Cetuximab plus radiation significantly reduced TICs growth under non‐differentiating conditions. Together, our findings provide evidence that ΔNp63α expression is regulated by EGFR activation through STAT3 and that the EGFR–ΔNp63α axis is crucial for proliferation of TICs present in SCCs. J. Cell. Physiol. 228: 871–878, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
35.
Silvio Schueler Stefan Kapeller Heino Konrad Thomas Geburek Michael Mengl Michele Bozzano Jarkko Koskela François Lefèvre Jason Hubert Hojka Kraigher Roman Longauer Ditte C. Olrik 《Biodiversity and Conservation》2013,22(5):1151-1166
Genetic resources of forest trees are considered as a key factor for the persistence of forest ecosystems because the ability of tree species to survive under changing climate depends strongly on their intraspecific variation in climate response. Therefore, utilizing available genetic variation in climate response and planting alternative provenances suitable for future climatic conditions is considered as an important adaptation measure for forestry. On the other hand, the distribution of adaptive genetic diversity of many tree species is still unknown and the predicted shift of ecological zones and species’ distribution may threaten forest genetic resources that are important for adaptation. Here, we use Norway spruce in Austria as a case study to demonstrate the genetic variation in climate response and to analyse the existing network of genetic conservation units for its effectiveness to safeguard the hotspots of adaptive and neutral genetic diversity of this species. An analysis of the climate response of 480 provenances, clustered into 9 groups of climatically similar provenances, revealed high variation among provenance groups. The most productive and promising provenance clusters for future climates originate from three regions that today depict the warmest and driest areas of the natural spruce distribution in Austria. Gap analysis of the Austrian genetic conservation units in the EUFGIS Portal suggests adequate coverage of the genetic hotspots in southern parts of Austria, but not in eastern and northern Austria. Therefore conservation measures and sustainable utilization of the valuable genetic resources in these regions need to be expanded to cover their high adaptive genetic variation and local adaptation to a warmer climate. The study shows that current conservation efforts need to be evaluated for their effectiveness to protect genetic resources that are important for the survival of trees in a future climate. 相似文献
36.
Marina Padroni Andrea Bernardoni Carmine Tamborino Gloria Roversi Massimo Borrelli Andrea Saletti Alessandro De Vito Cristiano Azzini Luca Borgatti Onofrio Marcello Christopher d’Esterre Stefano Ceruti Ilaria Casetta Ting-Yim Lee Enrico Fainardi 《PloS one》2016,11(1)
Introduction
The capability of CT perfusion (CTP) Alberta Stroke Program Early CT Score (ASPECTS) to predict outcome and identify ischemia severity in acute ischemic stroke (AIS) patients is still questioned.Methods
62 patients with AIS were imaged within 8 hours of symptom onset by non-contrast CT, CT angiography and CTP scans at admission and 24 hours. CTP ASPECTS was calculated on the affected hemisphere using cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) maps by subtracting 1 point for any abnormalities visually detected or measured within multiple cortical circular regions of interest according to previously established thresholds. MTT-CBV ASPECTS was considered as CTP ASPECTS mismatch. Hemorrhagic transformation (HT), recanalization status and reperfusion grade at 24 hours, final infarct volume at 7 days and modified Rankin scale (mRS) at 3 months after onset were recorded.Results
Semi-quantitative and quantitative CTP ASPECTS were highly correlated (p<0.00001). CBF, CBV and MTT ASPECTS were higher in patients with no HT and mRS≤2 and inversely associated with final infarct volume and mRS (p values: from p<0.05 to p<0.00001). CTP ASPECTS mismatch was slightly associated with radiological and clinical outcomes (p values: from p<0.05 to p<0.02) only if evaluated quantitatively. A CBV ASPECTS of 9 was the optimal semi-quantitative value for predicting outcome.Conclusions
Our findings suggest that visual inspection of CTP ASPECTS recognizes infarct and ischemic absolute values. Semi-quantitative CBV ASPECTS, but not CTP ASPECTS mismatch, represents a strong prognostic indicator, implying that core extent is the main determinant of outcome, irrespective of penumbra size. 相似文献37.
Daniel Maximo Correa Alcantara Camila Silveira Souza Gustavo Graciolli Silvio Shigueo Nihei 《Studies on Neotropical Fauna and Environment》2016,51(3):235-238
The selection of roosts is considered a critical factor to the survival of Noctilio albiventris. Thus, we located and identified N. albiventris day roosts in the Pantanal, near the Miranda River. We identified four species of tree: Banara arguta, Inga vera, Ocotea diospyrifolia and Vitex cymosa. Additional studies are important to understand the impact of specific requirements in the selection of roosts for Noctilio albiventris and to compare the observed patterns in different environments. 相似文献
38.
Annalisa?Barera Silvio?Buscemi Roberto?Monastero Calogero?Caruso Rosalia?Caldarella Marcello?CiaccioEmail author 《Immunity & ageing : I & A》2016,13(1):14
Background
It is well known that Mediterranean Diet can positively influence the health of each individual, in particular it is know that fibers have an important role. However, in Mediterranean cities most people do not have a close adherence to Mediterranean diet. Thus, in our study, we considered fibers like β-glucans that have been added to pasta with a percentage of 6 %. Our study aimed to evaluate the capacity of β-glucans intake on oxidative stress and inflammation in a cohort of middle aged slightly overweight subjects.Methods
We used a longitudinal study design. The study lasted 30 days during which time, each participant acted with no food restriction. Participants underwent morning fasting blood venous sample for blood chemistry and other biological parameters at the beginning of the study and after 30 days of pasta supplemented with 6 % of β-glucan intake 4 times a week. We performed anthropometric, biochemical, oxidative stress and cytokine analysis at the beginning and the end of study.Results
After the 30 days of pasta intake we obtained a significant decrease of LDL-cholesterol, IL-6 and AGEs levels.Conclusion
The results confirmed a capacity of β-glucans intake to lower oxidative stress. Additional longitudinal observation on community-based cohorts are needed to confirm these data and investigate the biological mechanisms through which effects are induced, and to fully explore the therapeutic potential of β-glucans.39.
Sasa Savic Silvio Keckes Zivomir Petronijevic 《Biocatalysis and Biotransformation》2016,34(5):226-235
Horseradish peroxidase is a well-known member of the peroxidase family that catalyzes oxidation of flavonoids and phenolic substrates to free phenoxyl or semiquinone radicals. Aim of this study was to investigate in vitro oxidation of quercetin by horseradish peroxidase in the presence of l-cysteine as nucleophilic agent, and its influence on previously formed semiquinone- and quinone-type metabolites. The obtained results showed that in the reaction without l-cysteine several products were present, such as quercetin quinone methide, phloroglucinol carboxylic acid, protocatechuic acid, as well as quercetin heterodimer and derivates of quercetin heterodimer. On the other hand, in the presence of l-cysteine only three products were obtained, quercetin quinone methide and two new isomeric mono-cysteine derivatives of quercetin with mass exp. m/z 420.04?±?0.1 [quercetin?+?cysteine–H]– (theor. m/z 420.0389 [quercetin?+?cysteine–H]–). 相似文献
40.