全文获取类型
收费全文 | 510篇 |
免费 | 29篇 |
出版年
2022年 | 2篇 |
2021年 | 3篇 |
2019年 | 4篇 |
2018年 | 9篇 |
2017年 | 5篇 |
2016年 | 7篇 |
2015年 | 8篇 |
2014年 | 18篇 |
2013年 | 21篇 |
2012年 | 30篇 |
2011年 | 32篇 |
2010年 | 14篇 |
2009年 | 10篇 |
2008年 | 22篇 |
2007年 | 33篇 |
2006年 | 25篇 |
2005年 | 24篇 |
2004年 | 28篇 |
2003年 | 38篇 |
2002年 | 30篇 |
2001年 | 21篇 |
2000年 | 17篇 |
1999年 | 20篇 |
1998年 | 7篇 |
1997年 | 6篇 |
1996年 | 12篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 8篇 |
1991年 | 11篇 |
1990年 | 7篇 |
1989年 | 4篇 |
1988年 | 9篇 |
1987年 | 5篇 |
1986年 | 2篇 |
1985年 | 8篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1978年 | 4篇 |
1977年 | 2篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1970年 | 2篇 |
1969年 | 1篇 |
1967年 | 5篇 |
1965年 | 1篇 |
排序方式: 共有539条查询结果,搜索用时 597 毫秒
81.
Ivano Bertini Frank Engelke Leonardo Gonnelli Benno Knott Claudio Luchinat David Osen Enrico Ravera 《Journal of biomolecular NMR》2012,54(2):123-127
We have recently proposed sedimented solute NMR (SedNMR) as a solid-state method to access biomolecules without the need of crystallization or other sample manipulation. The drawback of SedNMR is that samples are intrinsically diluted and this is detrimental for the signal intensity. Ultracentrifugal devices can be used to increase the amount of sample inside the rotor, overcoming the intrinsic sensitivity limitation of the method. We designed two different devices and we here report the directions for using such devices and the relevant equations for determining the parameters for sedimentation. 相似文献
82.
In addition to a remarkable sexual dimorphism of serum and urine proteomes, the rat is exceptional for the wide difference between the serum patterns during an acute phase reaction vs baseline conditions. This feature allows monitoring with high sensitivity onset and progression of any pathological state that involves an inflammatory component as well as assessing the outcome of any therapeutic intervention. Reference maps have been defined for the proteomes of serum, urine, cerebrospinal fluid and bronchoalveolar lavage fluid. For both serum and urine most of the proteomic investigations have dealt with toxicological testing, for BALF with allergic or irritative reactions, whereas with CSF the main aim was the characterization of rat models of neurological disorders. When surveying more than ten years of literature on rat biological fluid proteomics, it is puzzling to see how seldom a consistent analytical plan has been set up for the comparative investigation on two or more types of sample, whether to fully characterize a disease model or to evaluate pharmacological/toxicological effects of a drug. It is also regrettable that in several cases only a negligible part of the results is discussed at length whereas most data are not even made known to the scientific community. 相似文献
83.
84.
Glenn A. Marsh Carol de Jong Jennifer A. Barr Mary Tachedjian Craig Smith Deborah Middleton Meng Yu Shawn Todd Adam J. Foord Volker Haring Jean Payne Rachel Robinson Ivano Broz Gary Crameri Hume E. Field Lin-Fa Wang 《PLoS pathogens》2012,8(8)
The genus Henipavirus in the family Paramyxoviridae contains two viruses, Hendra virus (HeV) and Nipah virus (NiV) for which pteropid bats act as the main natural reservoir. Each virus also causes serious and commonly lethal infection of people as well as various species of domestic animals, however little is known about the associated mechanisms of pathogenesis. Here, we report the isolation and characterization of a new paramyxovirus from pteropid bats, Cedar virus (CedPV), which shares significant features with the known henipaviruses. The genome size (18,162 nt) and organization of CedPV is very similar to that of HeV and NiV; its nucleocapsid protein displays antigenic cross-reactivity with henipaviruses; and it uses the same receptor molecule (ephrin- B2) for entry during infection. Preliminary challenge studies with CedPV in ferrets and guinea pigs, both susceptible to infection and disease with known henipaviruses, confirmed virus replication and production of neutralizing antibodies although clinical disease was not observed. In this context, it is interesting to note that the major genetic difference between CedPV and HeV or NiV lies within the coding strategy of the P gene, which is known to play an important role in evading the host innate immune system. Unlike HeV, NiV, and almost all known paramyxoviruses, the CedPV P gene lacks both RNA editing and also the coding capacity for the highly conserved V protein. Preliminary study indicated that CedPV infection of human cells induces a more robust IFN-β response than HeV. 相似文献
85.
Nivea Cristina Sena Costa Fernanda Bertini Yasmin Rodarte Carvalho Janete Dias Almeida Ana Sueli Rodrigues Cavalcante 《Journal of medical case reports》2012,6(1):56
Introduction
Granular cell tumor is an uncommon neoplasm that can occur in any part of the body, including the orofacial region. The tumor is usually benign, but there are reports of cases in which the tumor shows a locally aggressive behavior, malignancy, and distant metastases. The most widely accepted hypothesis is that granular cell tumor arises from the altered metabolism of Schwann cells. The tumor is typically asymptomatic and appears as a nodule that does not exceed 3 cm.Case presentation
In case 1, a 26-year-old Caucasian man was seen at the Oral Medicine out-patient clinic of the São José dos Campos Dental School, Universidade Estadual Paulista, with a 'small blister on the tongue', which he had noted approximately three years ago. The nodule was located on the dorsum of the tongue, measured about 1.5 cm in diameter, and was not tender to palpation. Treatment consisted of an excisional biopsy performed on the basis of the diagnostic hypothesis of granular cell tumor, which was confirmed by microscopic analysis. In case 2, a 31-year-old Caucasian woman attended the out-patient clinic of the São José dos Campos Dental School, Universidade Estadual Paulista, with a five-year history of a 'painful lump on the tongue'. Intra-oral examination revealed the presence of a nodular lesion measuring approximately 0.8 cm in diameter, which was located deep in the submucosa of the right lateral margin of the tongue. Treatment consisted of an excisional biopsy performed on the basis of the differential diagnosis of neurofibroma and granular cell tumor. Microscopic analysis defined the final diagnosis of granular cell tumor.Conclusions
Granular cell tumor is an uncommon tumor that must be carefully diagnosed and treated correctly.86.
Sara Benedetti Pia Bernasconi Enrico Bertini Elena Biagini Giuseppe Boriani Cristina Capanni Nicola Carboni Giovanna Cenacchi Marta Columbaro Monica D’Adamo Adele D’Amico Maria Rosaria D’Apice Marianna Fontana Alessandra Gambineri Giovanna Lattanzi Rocco Liguori Nadir M Maraldi Laura Mazzanti Eugenio Mercuri Tiziana Mongini Lucia O Morandi Iria Neri Giovanni Nigro Giuseppe Novelli Michela Ortolani Renato Pasquali Antonella Pini Stefania Petrini Luisa Politano Stefano Previtali Lisa Pucci Claudio Rapezzi Giulia Ricci Carmelo Rodolico Paolo Sbraccia Emanuela Scarano Gabriele Siciliano Stefano Squarzoni Antonio Toscano Liliana Vercelli Matteo Ziacchi 《Orphanet journal of rare diseases》2012,7(1):1-3
The need for a collaborative approach to complex inherited diseases collectively referred to as laminopathies, encouraged Italian researchers, geneticists, physicians and patients to join in the Italian Network for Laminopathies, in 2009. Here, we highlight the advantages and added value of such a multidisciplinary effort to understand pathogenesis, clinical aspects and try to find a cure for Emery-Dreifuss muscular dystrophy, Mandibuloacral dysplasia, Hutchinson-Gilford Progeria and forms of lamin-linked cardiomyopathy, neuropathy and lipodystrophy. 相似文献
87.
88.
Ricchiuto P Rocco AG Gianazza E Corrada D Beringhelli T Eberini I 《Journal of molecular recognition : JMR》2008,21(5):348-354
Chicken liver bile acid binding protein (cL-BABP) crystallizes with water molecules in its binding site. To obtain insights on the role of internal water, we performed two 100 ns molecular dynamics (MD) simulations in explicit solvent for cL-BABP, as apo form and as a complex with two molecules of cholic acid, and analyzed in detail the dynamics properties of all water molecules. The diffusion coefficients of the more persistent internal water molecules are significantly different from the bulk, but similar between the two protein forms. A different number of molecules and a different organization are observed for apo- and holo-cL-BABP. Most water molecules identified in the binding site of the apo-crystal diffuse to the bulk during the simulation. In contrast, almost all the internal waters of the holo-crystal maintain the same interactions with internal sidechains and ligands, which suggests they have a relevant role in protein-ligand molecular recognition. Only in the presence of these water molecules we were able to reproduce, by a classical molecular docking approach, the structure of the complex cL-BABP::cholic acid with a low ligand root mean square deviation (RMSD) with respect to its reference positioning. Literature data reported a conserved pattern of hydrogen bonds between a single water molecule and three amino acid residues of the binding site in a series of crystallized FABP. In cL-BABP, the interactions between this conserved water molecule and the three residues are present in the crystal of both apo- and holo-cL-BABP but are lost immediately after the start of molecular dynamics. Copyright (c) 2008 John Wiley & Sons, Ltd. 相似文献
89.
90.
The Wilson disease protein or ATP7B is a P 1B-type ATPase involved in human copper homeostasis. The extended N-terminus of ATP7B protrudes into the cytosol and contains six Cu(I) binding domains. This report presents the NMR structure of the polypeptide consisting of soluble Cu(I) binding domains 3 and 4. The two domains exhibit ferredoxin-like folds, are linked by a flexible loop, and act independently of one another. Domains 3 and 4 tend to aggregate in a concentration-dependent manner involving nonspecific intermolecular interactions. Both domains can be loaded with Cu(I) when provided as an acetonitrile complex or by the chaperone HAH1. HAH1 forms a 70% complex with domain 4 that is in fast exchange with the free protein in solution. The ability of HAH1 to form a complex only with some domains of ATP7B is an interesting property of this class of proteins and may have a signaling role in the function of the ATPases. 相似文献