全文获取类型
收费全文 | 3007篇 |
免费 | 260篇 |
出版年
2023年 | 5篇 |
2022年 | 25篇 |
2021年 | 65篇 |
2020年 | 33篇 |
2019年 | 50篇 |
2018年 | 79篇 |
2017年 | 62篇 |
2016年 | 93篇 |
2015年 | 160篇 |
2014年 | 170篇 |
2013年 | 227篇 |
2012年 | 287篇 |
2011年 | 253篇 |
2010年 | 183篇 |
2009年 | 149篇 |
2008年 | 212篇 |
2007年 | 180篇 |
2006年 | 177篇 |
2005年 | 150篇 |
2004年 | 136篇 |
2003年 | 110篇 |
2002年 | 108篇 |
2001年 | 31篇 |
2000年 | 24篇 |
1999年 | 32篇 |
1998年 | 34篇 |
1997年 | 19篇 |
1996年 | 16篇 |
1995年 | 16篇 |
1994年 | 15篇 |
1993年 | 15篇 |
1992年 | 13篇 |
1991年 | 8篇 |
1990年 | 8篇 |
1989年 | 11篇 |
1988年 | 8篇 |
1987年 | 7篇 |
1986年 | 7篇 |
1985年 | 9篇 |
1984年 | 9篇 |
1983年 | 9篇 |
1982年 | 4篇 |
1975年 | 3篇 |
1971年 | 3篇 |
1970年 | 4篇 |
1969年 | 7篇 |
1968年 | 8篇 |
1967年 | 6篇 |
1966年 | 6篇 |
1965年 | 4篇 |
排序方式: 共有3267条查询结果,搜索用时 506 毫秒
241.
242.
243.
Pinkhasov J Alvarez ML Rigano MM Piensook K Larios D Pabst M Grass J Mukherjee P Gendler SJ Walmsley AM Mason HS 《Plant biotechnology journal》2011,9(9):991-1001
The human epithelial mucin MUC1 is a heavily glycosylated transmembrane protein that is overexpressed and aberrantly glycosylated on over 90% of human breast cancers. The altered glycosylation of MUC1 reveals an immunodominant peptide along its tandem repeat (TR) that has been used as a target for tumour immunotherapy. In this study, we used the MUC1 TR peptide as a test antigen to determine whether a plant-expressed human tumour-associated antigen can be successfully expressed in a plant system and whether it will be able to break self-antigen tolerance in a MUC1-tolerant mouse model. We report the expression of MUC1 TR peptide fused to the mucosal-targeting Escherichia coli enterotoxin B subunit (LTB-MUC1) in a plant host. Utilizing a rapid viral replicon transient expression system, we obtained high yields of LTB-MUC1. Importantly, the LTB-MUC1 fusion protein displayed post-translational modifications that affected its antigenicity. Glycan analysis revealed that LTB-MUC1 was glycosylated and a MUC1-specific monoclonal antibody detected only the glycosylated forms. A thorough saccharide analysis revealed that the glycans are tri-arabinans linked to hydroxyprolines within the MUC1 tandem repeat sequence. We immunized MUC1-tolerant mice (MUC1.Tg) with transiently expressed LTB-MUC1, and observed production of anti-MUC1 serum antibodies, indicating breach of tolerance. The results indicate that a plant-derived human tumour-associated antigen is equivalent to the human antigen in the context of immune recognition. 相似文献
244.
245.
Lorente M Torres S Salazar M Carracedo A Hernández-Tiedra S Rodríguez-Fornés F García-Taboada E Meléndez B Mollejo M Campos-Martín Y Barcia JA Guzmán M Velasco G 《Autophagy》2011,7(9):1071-1073
Δ?-tetrahydrocannabinol (THC), the main active component of marijuana, promotes cancer cell death via autophagy stimulation. We find that activation of the tyrosine kinase receptor ALK by its ligand midkine interferes with the signaling mechanism by which THC promotes autophagy-mediated glioma cell death. 相似文献
246.
Determining distances to objects is one of the most ubiquitous perceptual tasks in everyday life. Nevertheless, it is challenging because the information from a single image confounds object size and distance. Though our brains frequently judge distances accurately, the underlying computations employed by the brain are not well understood. Our work illuminates these computions by formulating a family of probabilistic models that encompass a variety of distinct hypotheses about distance and size perception. We compare these models' predictions to a set of human distance judgments in an interception experiment and use Bayesian analysis tools to quantitatively select the best hypothesis on the basis of its explanatory power and robustness over experimental data. The central question is: whether, and how, human distance perception incorporates size cues to improve accuracy. Our conclusions are: 1) humans incorporate haptic object size sensations for distance perception, 2) the incorporation of haptic sensations is suboptimal given their reliability, 3) humans use environmentally accurate size and distance priors, 4) distance judgments are produced by perceptual "posterior sampling". In addition, we compared our model's estimated sensory and motor noise parameters with previously reported measurements in the perceptual literature and found good correspondence between them. Taken together, these results represent a major step forward in establishing the computational underpinnings of human distance perception and the role of size information. 相似文献
247.
Giuseppe Battaglia Milena Cannella Barbara Riozzi Sara Orobello Marion L. Maat‐Schieman Eleonora Aronica Carla Letizia Busceti Andrea Ciarmiello Silvia Alberti Enrico Amico Jenny Sassone Simonetta Sipione Valeria Bruno Luigi Frati Ferdinando Nicoletti Ferdinando Squitieri 《Journal of cellular and molecular medicine》2011,15(3):555-571
A defective expression or activity of neurotrophic factors, such as brain‐ and glial‐derived neurotrophic factors, contributes to neuronal damage in Huntington’s disease (HD). Here, we focused on transforming growth factor‐β (TGF‐β1), a pleiotropic cytokine with an established role in mechanisms of neuroprotection. Asymptomatic HD patients showed a reduction in TGF‐β1 levels in the peripheral blood, which was related to trinucleotide mutation length and glucose hypometabolism in the caudate nucleus. Immunohistochemical analysis in post‐mortem brain tissues showed that TGF‐β1 was reduced in cortical neurons of asymptomatic and symptomatic HD patients. Both YAC128 and R6/2 HD mutant mice showed a reduced expression of TGF‐β1 in the cerebral cortex, localized in neurons, but not in astrocytes. We examined the pharmacological regulation of TGF‐β1 formation in asymptomatic R6/2 mice, where blood TGF‐β1 levels were also reduced. In these R6/2 mice, both the mGlu2/3 metabotropic glutamate receptor agonist, LY379268, and riluzole failed to increase TGF‐β1 formation in the cerebral cortex and corpus striatum, suggesting that a defect in the regulation of TGF‐β1 production is associated with HD. Accordingly, reduced TGF‐β1 mRNA and protein levels were found in cultured astrocytes transfected with mutated exon 1 of the human huntingtin gene, and in striatal knock‐in cell lines expressing full‐length huntingtin with an expanded glutamine repeat. Taken together, our data suggest that serum TGF‐β1 levels are potential biomarkers of HD development during the asymptomatic phase of the disease, and raise the possibility that strategies aimed at rescuing TGF‐β1 levels in the brain may influence the progression of HD. 相似文献
248.
249.
250.
Manuela Murariu Ecaterina Stela Dragan Adriana Adochitei Gheorghita Zbancioc Gabi Drochioiu 《Journal of peptide science》2011,17(7):512-519
The role of silver ions in various pathologies, as well as their effect on peptide conformation and properties are less understood. Consequently, we synthesized several peptides with various residues in their sequence to investigate silver‐induced conformational changes at various pH values by Circular Dichroism spectroscopy. Uniquely, the glycine‐based, histidine‐containing peptide showed a severe change from a random coil and β‐turn conformation to large α‐helices during silver binding. When comparing the effect of silver ions on the conformation of bradykinin a similar tendency was found. Besides, silver ions reduced the amyloid‐β peptide tendency to aggregation. Our results suggest a specific and protective role for silver ions in brain pathologies, which is related to their high affinity toward physiologically and pharmacologically active peptides. Fourier transform infrared spectroscopy studies as well as the mass spectrometric ones support our conclusions. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd. 相似文献