全文获取类型
收费全文 | 897篇 |
免费 | 51篇 |
专业分类
948篇 |
出版年
2023年 | 1篇 |
2022年 | 4篇 |
2021年 | 9篇 |
2020年 | 6篇 |
2019年 | 13篇 |
2018年 | 12篇 |
2017年 | 18篇 |
2016年 | 25篇 |
2015年 | 52篇 |
2014年 | 48篇 |
2013年 | 58篇 |
2012年 | 99篇 |
2011年 | 75篇 |
2010年 | 51篇 |
2009年 | 36篇 |
2008年 | 70篇 |
2007年 | 59篇 |
2006年 | 37篇 |
2005年 | 43篇 |
2004年 | 48篇 |
2003年 | 35篇 |
2002年 | 29篇 |
2001年 | 5篇 |
2000年 | 12篇 |
1999年 | 4篇 |
1998年 | 11篇 |
1997年 | 6篇 |
1996年 | 7篇 |
1995年 | 7篇 |
1994年 | 6篇 |
1993年 | 5篇 |
1992年 | 5篇 |
1991年 | 5篇 |
1990年 | 2篇 |
1987年 | 3篇 |
1986年 | 7篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 4篇 |
1977年 | 3篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1971年 | 1篇 |
1937年 | 1篇 |
排序方式: 共有948条查询结果,搜索用时 15 毫秒
11.
Aurelio Ciancio Mariantonietta Colagiero Laura Cristina Rosso Santos Nelida Murga Gutierrez Gaetano Grasso 《Mycoscience》2013,54(5):378-386
A new species of Hirsutella was isolated from unidentified mites on Petri plates inoculated with soil and root fragments collected from asparagus rhizosphere at Virú, Northern Peru. The fungus differs from other Hirsutella species by an envelope surrounding the conidium, conidia dimension and DNA sequences. In PDA cultures, the mycelium produced aerial hyphae with conidiogenous cells mainly at right angles, occasionally showing a secondary conidiophore. The solitary conidia are cymbiform, slightly apiculate, 5.0–6.0 × 3.0–4.0 μm. Phylogenetic analyses with partial rRNA and β-tubulin gene sequences confirmed the fungus as an Hirsutella (Ophiocordycipitaceae). Closest species shown by maximum likelihood and neighbor-joining trees were H. nodulosa and H. aphidis, from which the new species differs for conidium or conidiogenous cells dimensions, lack of synnemata and host type. A recombination event was also detected in the rRNA of the holotype strain, involving Ophiocordyceps sinensis as major parent and O. cochlidiicola as minor parent. A complement, inverted insertion was also found in its rRNA, involving part of the ITS2 and 5.8S regions, flanked by two short nucleotide arrays. Due to conidia dimension and phylogenetic position, the fungus is described as Hirsutella tunicata sp. nov. A review of mononematous Hirsutella species is provided. 相似文献
12.
Neurodegenerative diseases are associated with misfolding and deposition of specific proteins, either intra or extracellularly in the nervous system. Advanced glycation end products (AGEs) originate from different molecular species that become glycated after exposure to sugars. Several proteins implicated in neurodegenerative diseases have been found to be glycated in vivo and the extent of glycation is related to the pathologies of the patients. Although it is now accepted that there is a direct correlation between AGEs formation and the development of neurodegenerative diseases, several questions still remain unanswered: whether glycation is the triggering event or just an additional factor acting on the aggregation pathway. To this concern, in the present study we have investigated the effect of glycation on the aggregation pathway of the amyloidogenic W7FW14F apomyoglobin. Although this protein has not been related to any amyloid disease, it represents a good model to resemble proteins that intrinsically evolve toward the formation of amyloid aggregates in physiological conditions. We show that D-ribose, but not D-glucose, rapidly induces the W7FW14F apomyoglobin to generate AGEs in a time-dependent manner and protein ribosylation is likely to involve lysine residues on the polypeptide chain. Ribosylation of the W7FW14F apomyoglobin strongly affects its aggregation kinetics producing amyloid fibrils within few days. Cytotoxicity of the glycated aggregates has also been tested using a cell viability assay. We propose that ribosylation in the W7FW14F apomyoglobin induces the formation of a cross-link that strongly reduces the flexibility of the H helix and/or induce a conformational change that favor fibril formation. These results open new perspectives for AGEs biological role as they can be considered not only a triggering factor in amyloidosis but also a player in later stages of the aggregation process. 相似文献
13.
14.
15.
Annalisa Vilasi Silvia Vilasi Rocco Romano Fausto Acernese Fabrizio Barone Maria Luisa Balestrieri Rosa Maritato Gaetano Irace Ivana Sirangelo 《Journal of cellular physiology》2013,228(6):1359-1367
A range of debilitating human diseases is known to be associated with the formation of stable highly organized protein aggregates known as amyloid fibrils. The early prefibrillar aggregates behave as cytotoxic agents and their toxicity appears to result from an intrinsic ability to impair fundamental cellular processes by interacting with cellular membranes, causing oxidative stress and increase in free Ca2+ that lead to apoptotic or necrotic cell death. However, specific signaling pathways that underlie amyloid pathogenicity remain still unclear. This work aimed to clarify cell impairment induced by amyloid aggregated. To this end, we used a combined proteomic and one‐dimensional 1H‐NMR approach on NIH‐3T3 cells exposed to prefibrillar aggregates from the amyloidogenic apomyoglobin mutant W7FW14F. The results indicated that cell exposure to prefibrillar aggregates induces changes of the expression level of proteins and metabolites involved in stress response. The majority of the proteins and metabolites detected are reported to be related to oxidative stress, perturbation of calcium homeostasis, apoptotic and survival pathways, and membrane damage. In conclusion, the combined proteomic and 1H‐NMR metabonomic approach, described in this study, contributes to unveil novel proteins and metabolites that could take part to the general framework of the toxicity induced by amyloid aggregates. These findings offer new insights in therapeutic and diagnostic opportunities. J. Cell. Physiol. 228: 1359–1367, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
16.
Erik Procko Rickard Hedman Keith Hamilton Jayaraman Seetharaman Sarel J. Fleishman Min Su James Aramini Gregory Kornhaber John F. Hunt Liang Tong Gaetano T. Montelione David Baker 《Journal of molecular biology》2013
While there has been considerable progress in designing protein–protein interactions, the design of proteins that bind polar surfaces is an unmet challenge. We describe the computational design of a protein that binds the acidic active site of hen egg lysozyme and inhibits the enzyme. The design process starts with two polar amino acids that fit deep into the enzyme active site, identifies a protein scaffold that supports these residues and is complementary in shape to the lysozyme active-site region, and finally optimizes the surrounding contact surface for high-affinity binding. Following affinity maturation, a protein designed using this method bound lysozyme with low nanomolar affinity, and a combination of NMR studies, crystallography, and knockout mutagenesis confirmed the designed binding surface and orientation. Saturation mutagenesis with selection and deep sequencing demonstrated that specific designed interactions extending well beyond the centrally grafted polar residues are critical for high-affinity binding. 相似文献
17.
Luciano Pirone Luigi Vitagliano Sonia Di Gaetano Emilia Pedone 《Journal of molecular recognition : JMR》2013,26(10):488-495
Recent investigations have shown that members of the KCTD family play important roles in fundamental biological processes. Despite their roles, very limited information is available on their structures and molecular organization. By combining different experimental and theoretical techniques, we have here characterized the two folded domains of KCTD12, an integral component and modulator of the GABAB2 receptor. Secondary prediction methods and CD spectroscopy have shown that the N‐terminal domain KCTD12BTB assumes an α/β structure, whereas the C‐terminal domain KCTD12H1 is predominantly characterized by a β‐structure. Binding assays indicate that the two domains independently expressed show a good affinity for each other. This suggests that the overall protein is likely endowed with a rather compact structure with two interacting structured domains joint by a long disordered region. Notably, both KCTD12BTB and KCTD12H1 are tetrameric when individually expressed. This finding could modify the traditional view that ascribes only to POZ/BTB domain a specific oligomerization role. The first quantification of the affinity of KCTD12POZ/BTB for the C‐terminal region of GABAB2 shows that it falls in the low micromolar range. Interestingly, we also demonstrate that a GABAB2‐related peptide is able to bind KCTD12BTB with a very high affinity. This peptide may represent a useful tool for modulating KCTD12/GABAB2 interaction in vitro and may also constitute the starting point for the development of peptidomimetic compounds with a potential for therapeutic applications. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
18.
Sihem Dabbou Samia Dabbou Guido Flamini Gaetano Pandino Laura Gasco Ahmed Noureddine Helal 《化学与生物多样性》2016,13(11):1475-1483
The phytochemical composition in two Tunisian globe artichoke cultivars (bracts, leaves, and floral stems) was evaluated in the plant byproducts. The results indicated that the bracts contain the highest levels of total phenols, o‐diphenols, and flavonoids, whereas tannins seem to be more abundant in the leaves. Bracts from the ‘Violet d'Hyères’ cultivar possessed more total phenols (160.8 mg/g DW), flavonoids (64.9 mg/g DW), and anthocyanins (15.3 μg/g DW) than the ‘Blanc d'Oran’ bracts (134.5 mg/g DW, 51.2 mg/g DW, and 8.3 μg/g DW, resp.). Sixty‐four volatile compounds were identified in the headspace of globe artichoke material, particularly in the bracts. The volatile profile showed that sesquiterpene hydrocarbons and non‐terpene derivatives were the main volatiles emitted by the bracts in both cultivars. These results suggest that globe artichoke byproducts might represent a potential source of natural compounds, which could be used as nutraceuticals or as ingredients in the design of functional foods. 相似文献
19.
20.
Gaetano M. Gargiulo Federica Gemelli Giuseppe Cambrea Giusy Bonanno Ferraro Alice Crosca 《Phycological Research》2019,67(1):72-76
This study focused on a method based on the capacity of cationic dyes to stain only the nucleus and chromosomes in cells subjected to either acid or alkaline hydrolysis. The method and the squash were optimized for the Characeae and were described in detail. Nuclei from vegetative shoot apices and antheridial filament cells of unfixed, fixed and herbarium material of Nitella opaca were investigated using the Azure A or Toulidine Blue stains. Comparisons with some other staining methods, used in the previous studies, were also reported. The Azure A/Toulidine Blue method is useful to obtain clear images of chromosome morphology comparable or higher to that obtained with Feulgen or Aceto‐Orcein. It requires little time and a less complicated procedure in comparison with other staining methods. 相似文献