全文获取类型
收费全文 | 738篇 |
免费 | 62篇 |
出版年
2022年 | 2篇 |
2021年 | 15篇 |
2020年 | 7篇 |
2019年 | 10篇 |
2018年 | 17篇 |
2017年 | 19篇 |
2016年 | 19篇 |
2015年 | 37篇 |
2014年 | 46篇 |
2013年 | 64篇 |
2012年 | 60篇 |
2011年 | 61篇 |
2010年 | 33篇 |
2009年 | 27篇 |
2008年 | 42篇 |
2007年 | 42篇 |
2006年 | 41篇 |
2005年 | 54篇 |
2004年 | 35篇 |
2003年 | 39篇 |
2002年 | 33篇 |
2001年 | 6篇 |
2000年 | 3篇 |
1999年 | 7篇 |
1998年 | 9篇 |
1997年 | 9篇 |
1996年 | 8篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 8篇 |
1991年 | 1篇 |
1990年 | 6篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1985年 | 4篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 2篇 |
1976年 | 2篇 |
1971年 | 1篇 |
1969年 | 1篇 |
1966年 | 2篇 |
1965年 | 1篇 |
1953年 | 1篇 |
排序方式: 共有800条查询结果,搜索用时 137 毫秒
151.
152.
Jure Pohleven Nataša Obermajer Jerica Sabotič Sabina Anžlovar Kristina Sepčić Janko Kos Bogdan Kralj Borut Štrukelj Jože Brzin 《Biochimica et Biophysica Acta (BBA)/General Subjects》2009
Background
Lectins are a diverse group of carbohydrate-binding proteins exhibiting numerous biological activities and functions.Methods
Two-step serial carbohydrate affinity chromatography was used to isolate a lectin from the edible mushroom clouded agaric (Clitocybe nebularis). It was characterized biochemically, its gene and cDNA cloned and the deduced amino acid sequence analyzed. Its activity was tested by hemagglutination assay and carbohydrate-binding specificity determined by glycan microarray analysis. Its effect on proliferation of several human cell lines was determined by MTS assay.Results
A homodimeric lectin with 15.9-kDa subunits agglutinates human group A, followed by B, O, and bovine erythrocytes. Hemagglutination was inhibited by glycoprotein asialofetuin and lactose. Glycan microarray analysis revealed that the lectin recognizes human blood group A determinant GalNAcα1–3(Fucα1–2)Galβ-containing carbohydrates, and GalNAcβ1–4GlcNAc (N,N'-diacetyllactosediamine). The lectin exerts antiproliferative activity specific to human leukemic T cells.Conclusions
The protein belongs to the ricin B-like lectin superfamily, and has been designated as C. nebularis lectin (CNL). Its antiproliferative effect appears to be elicited by binding to carbohydrate receptors on human leukemic T cells.General significance
CNL is one of the few mushroom ricin B-like lectins that have been identified and the only one so far shown to possess immunomodulatory properties. 相似文献153.
Richard Kraemer Philipp Latzin Isabelle Pramana Pietro Ballinari Sabina Gallati Urs Frey 《Respiratory research》2009,10(1):106
Background and Aim
In patients with cystic fibrosis (CF) the architecture of the developing lungs and the ventilation of lung units are progressively affected, influencing intrapulmonary gas mixing and gas exchange. We examined the long-term course of blood gas measurements in relation to characteristics of lung function and the influence of different CFTR genotype upon this process.Methods
Serial annual measurements of PaO2 and PaCO2 assessed in relation to lung function, providing functional residual capacity (FRCpleth), lung clearance index (LCI), trapped gas (VTG), airway resistance (sReff), and forced expiratory indices (FEV1, FEF50), were collected in 178 children (88 males; 90 females) with CF, over an age range of 5 to 18 years. Linear mixed model analysis and binary logistic regression analysis were used to define predominant lung function parameters influencing oxygenation and carbon dioxide elimination.Results
PaO2 decreased linearly from age 5 to 18 years, and was mainly associated with FRCpleth, (p < 0.0001), FEV1 (p < 0.001), FEF50 (p < 0.002), and LCI (p < 0.002), indicating that oxygenation was associated with the degree of pulmonary hyperinflation, ventilation inhomogeneities and impeded airway function. PaCO2 showed a transitory phase of low PaCO2 values, mainly during the age range of 5 to 12 years. Both PaO2 and PaCO2 presented with different progression slopes within specific CFTR genotypes.Conclusion
In the long-term evaluation of gas exchange characteristics, an association with different lung function patterns was found and was closely related to specific genotypes. Early examination of blood gases may reveal hypocarbia, presumably reflecting compensatory mechanisms to improve oxygenation. 相似文献154.
In this paper, expanding on a well-known connection between Whittaker's beta diversity and multivariate dissimilarity coefficients, a simple test for differences in beta diversity among different sets of plots is proposed. Being based on any suitable (not necessarily symmetric) plot-to-plot dissimilarity coefficient the test is appropriate for analyzing multivariate data that are usually zero-inflated due to the large number of rare species and for which the number of variables (species) is typically larger than the number of observations (plots). To illustrate the proposed test in practice, we used data from two beech forests with different management history in Abruzzo (central Italy). 相似文献
155.
Venkata Sabbisetti Arianna Di Napoli Apryle Seeley Angela M. Amato Esther O'Regan Musie Ghebremichael Massimo Loda Sabina Signoretti 《PloS one》2009,4(6)
There is increasing evidence that p63, and specifically ΔNp63, plays a central role in both development and tumorigenesis by promoting epithelial cell survival. However, few studies have addressed the molecular mechanisms through which such important function is exerted. Fatty acid synthase (FASN), a key enzyme that synthesizes long-chain fatty acids and is involved in both embryogenesis and cancer, has been recently proposed as a direct target of p53 family members, including p63 and p73. Here we show that knockdown of either total or ΔN-specific p63 isoforms in squamous cell carcinoma (SCC9) or immortalized prostate epithelial (iPrEC) cells caused a decrease in cell viability by inducing apoptosis without affecting the cell cycle. p63 silencing significantly reduced both the expression and the activity of FASN. Importantly, stable overexpression of either FASN or myristoylated AKT (myr-AKT) was able to partially rescue cells from cell death induced by p63 silencing. FASN induced AKT phosphorylation and a significant reduction in cell viability was observed when FASN-overexpressing SCC9 cells were treated with an AKT inhibitor after p63 knockdown, indicating that AKT plays a major role in FASN-mediated survival. Activated AKT did not cause any alteration in the FASN protein levels but induced its activity, suggesting that the rescue from apoptosis documented in the p63-silenced cells expressing myr-AKT cells may be partially mediated by FASN. Finally, we demonstrated that p63 and FASN expression are positively associated in clinical squamous cell carcinoma samples as well as in the developing prostate. Taken together, our findings demonstrate that FASN is a functionally relevant target of p63 and is required for mediating its pro-survival effects. 相似文献
156.
Background
Regulatory T-cells (Tregs), characterized as CD4+CD25hi T-cells expressing FOXP3, play a crucial role in controlling healthy immune development during early immune maturation. Recently, FOXP3 demethylation was suggested to be a novel marker for natural Tregs in adults. In cord blood, the role and function of Tregs and its demethylation is poorly understood. We assessed FOXP3 demethylation in cord blood in relation to previously used Treg markers such as CD4+CD25hi, FOXP3 mRNA, protein expression, and suppressive Treg function.Methodology
Cord blood mononuclear cells (CBMC) were isolated from 70 healthy neonates, stimulated for 3 days with the microbial stimulus lipid A (LpA), and allergen Dermatophagoides pteronyssinus (Derp1). Tregs (CD4+CD25hi, intracellular, mRNA FOXP3 expression, isolated cells), DNA methylation of the FOXP3-locus and suppressive Treg function were assessed.Principal Findings
Demethylation of FOXP3 in whole blood was specific for isolated CD4+CD25hi Tregs. Demethylation of FOXP3 was positively correlated with unstimulated and LpA-stimulated FOXP3 mRNA-expression (p≤0.05), and CD4+CD25hi T-cells (p≤0.03). Importantly, increased FOXP3 demethylation correlated with more efficient suppressive capacity of Tregs (r = 0.72, p = 0.005). Furthermore, FOXP3 demethylation was positively correlated with Th2 cytokines (IL-5, IL-13) following LpA-stimulation (p = 0.006/0.04), with Th2 and IL-17 following Derp1+LpA-stimulations (p≤0.009), but not Th1 cytokines (IFN-γ).Conclusions
FOXP3 demethylation reliable quantifies Tregs in cord blood. FOXP3 demethylation corresponds well with the suppressive potential of Tregs. The resulting strict correlation with functionally suppressive Tregs and the relative ease of measurement render it into a valuable novel marker for large field studies assessing Tregs as qualitative marker indicative of functional activity. 相似文献157.
Fargol Mazaheri Nicolas Snaidero Gernot Kleinberger Charlotte Madore Anna Daria Georg Werner Susanne Krasemann Anja Capell Dietrich Trümbach Wolfgang Wurst Bettina Brunner Sebastian Bultmann Sabina Tahirovic Martin Kerschensteiner Thomas Misgeld Oleg Butovsky Christian Haass 《EMBO reports》2017,18(7):1186-1198
158.
Marianyela Sabina Petrizzelli Dominique de Vienne Thibault Nidelet Camille Noûs Christine Dillmann 《PLoS computational biology》2021,17(7)
The relationship between different levels of integration is a key feature for understanding the genotype-phenotype map. Here, we describe a novel method of integrated data analysis that incorporates protein abundance data into constraint-based modeling to elucidate the biological mechanisms underlying phenotypic variation. Specifically, we studied yeast genetic diversity at three levels of phenotypic complexity in a population of yeast obtained by pairwise crosses of eleven strains belonging to two species, Saccharomyces cerevisiae and S. uvarum. The data included protein abundances, integrated traits (life-history/fermentation) and computational estimates of metabolic fluxes. Results highlighted that the negative correlation between production traits such as population carrying capacity (K) and traits associated with growth and fermentation rates (Jmax) is explained by a differential usage of energy production pathways: a high K was associated with high TCA fluxes, while a high Jmax was associated with high glycolytic fluxes. Enrichment analysis of protein sets confirmed our results.This powerful approach allowed us to identify the molecular and metabolic bases of integrated trait variation, and therefore has a broad applicability domain. 相似文献
159.
160.
Górska-Frączek S Sandström C Kenne L Rybka J Strus M Heczko P Gamian A 《Carbohydrate research》2011,346(18):2926-2932
A novel structure of exopolysaccharide from the lactic acid bacteria (LAB) Lactobacillus rhamnosus KL37B, from the human intestinal flora, is described. During the structural investigation of the exopolysaccharide it was found that the repeating unit is a nonasaccharide, which is the largest repeating unit found in LAB exopolysaccharides to date. The polysaccharide material was prepared by TCA extraction of a bacterial cell mass, purified by anion-exchange and gel permeation chromatography and characterized using chemical and enzymatic methods. On the basis of monosaccharide and methylation analysis and also 1D and 2D 1H and 13C NMR spectroscopy the exopolysaccharide was shown to be composed of the following nonasaccharide repeating unit:The physicochemical cell surface study and adhesive properties indicated distinct surface properties of Lactobacillus rhamnosus strain KL37B with high adhesive abilities to Caco-2 cells, hydrophobicity and slime production, in comparison to other Lactobacillus strains used as controls. 相似文献