全文获取类型
收费全文 | 3087篇 |
免费 | 199篇 |
出版年
2024年 | 3篇 |
2023年 | 25篇 |
2022年 | 63篇 |
2021年 | 97篇 |
2020年 | 44篇 |
2019年 | 75篇 |
2018年 | 92篇 |
2017年 | 76篇 |
2016年 | 119篇 |
2015年 | 199篇 |
2014年 | 193篇 |
2013年 | 210篇 |
2012年 | 337篇 |
2011年 | 266篇 |
2010年 | 166篇 |
2009年 | 157篇 |
2008年 | 199篇 |
2007年 | 205篇 |
2006年 | 163篇 |
2005年 | 140篇 |
2004年 | 106篇 |
2003年 | 91篇 |
2002年 | 103篇 |
2001年 | 12篇 |
2000年 | 7篇 |
1999年 | 18篇 |
1998年 | 10篇 |
1997年 | 9篇 |
1996年 | 5篇 |
1995年 | 13篇 |
1994年 | 3篇 |
1993年 | 11篇 |
1992年 | 11篇 |
1991年 | 7篇 |
1990年 | 8篇 |
1989年 | 4篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1985年 | 4篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1972年 | 3篇 |
1967年 | 1篇 |
排序方式: 共有3286条查询结果,搜索用时 359 毫秒
991.
Giordano D Russo R Ciaccio C Howes BD di Prisco G Marden MC Hui Bon Hoa G Smulevich G Coletta M Verde C 《IUBMB life》2011,63(7):566-573
The spectroscopic and ligand-binding properties of a 2/2 globin from the Antarctic bacterium Pseudoalteromonas haloplanktis TAC125 have been studied in the ferrous state. It displays two major conformations characterized by CO-association rates that differ by a factor of 20, with relative fractions that depend on pH. A dynamic equilibrium is found between the two conformations, as indicated by an enhanced slower phase when lower CO levels were used to allow a longer time to facilitate the transition. The deoxy form, in the absence of external ligands, is a mixture of a predominant six-coordinate low spin form and a five-coordinate high-spin state; the proportion of low spin increasing at alkaline pH. In addition, at temperatures above the physiological temperature of 1 °C, an enhanced tendency of the protein to oxidize is observed. 相似文献
992.
Pesce A Tilleman L Dewilde S Ascenzi P Coletta M Ciaccio C Bruno S Moens L Bolognesi M Nardini M 《IUBMB life》2011,63(5):287-294
Protoglobin from Methanosarcina acetivorans C2A (MaPgb), a strictly anaerobic methanogenic Archaea, displays peculiar structural and functional properties within members of the hemoglobin superfamily. In fact, MaPgb-specific loops and a N-terminal extension (20 amino acid residues) completely bury the heme within the protein matrix. Therefore, the access of diatomic gaseous molecules to the heme is granted by two apolar tunnels reaching the heme distal site from locations at the B/G and B/E helix interfaces. The presence of two tunnels within the protein matrix could be partly responsible for the slightly biphasic ligand binding behavior. Unusually, MaPgb oxygenation is favored with respect to carbonylation. Here, the crucial role of Tyr(B10)61 and Ile(G11)149 residues, located in the heme distal site and lining the protein matrix tunnels 1 and 2, respectively, on ligand binding to the heme-Fe-atom and on distal site structural organization is reported. In particular, tunnel 1 accessibility is modulated by a complex reorganization of the Trp(B9)60 and Phe(E11)93 side-chains, triggered by mutations of the Tyr(B10)61 and Ile(G11)149 residues, and affected by the presence and type of the distal heme-bound ligand. 相似文献
993.
Chicatun F Pedraza CE Ghezzi CE Marelli B Kaartinen MT McKee MD Nazhat SN 《Biomacromolecules》2011,12(8):2946-2956
Bone extracellular matrix (ECM) is a 3D network, composed of collagen type I and a number of other macromolecules, including glycosaminoglycans (GAGs), which stimulate signaling pathways that regulate osteoblast growth and differentiation. To model the ECM of bone for tissue regenerative approaches, dense collagen/chitosan (Coll/CTS) hybrid hydrogels were developed using different proportions of CTS to mimic GAG components of the ECM. MC3T3-E1 mouse calvaria preosteoblasts were seeded within plastically compressed Coll/CTS hydrogels with solid content approaching that of native bone osteoid. Dense, cellular Coll/CTS hybrids were maintained for up to 8 weeks under either basal or osteogenic conditions. Higher CTS content significantly increased gel resistance to collagenase degradation. The incorporation of CTS to collagen gels decreased the apparent tensile modulus from 1.82 to 0.33 MPa. In contrast, the compressive modulus of Coll/CTS hybrids increased in direct proportion to CTS content exhibiting an increase from 23.50 to 55.25 kPa. CTS incorporation also led to an increase in scaffold resistance to cell-induced contraction. MC3T3-E1 viability, proliferation, and matrix remodeling capability (via matrix metalloproteinase expression) were maintained. Alkaline phosphatase activity was increased up to two-fold, and quantification of phosphate mineral deposition was significantly increased with CTS incorporation. Thus, dense Coll/CTS scaffolds provide osteoid-like models for the study of osteoblast differentiation and bone tissue engineering. 相似文献
994.
995.
Sergio Giuffrida Rosario Troia Chiara Schiraldi Antonella D??Agostino Mario De Rosa Lorenzo Cordone 《Food biophysics》2011,6(2):217-226
Saccharide-based biopreservation is widely studied because of its scientific importance and possible technological outcomes
for food and pharmaceutical industries. Ternary protein/saccharide/water systems have been extensively exploited to model
the characteristics of the in vivo biopreservation process. A tight, water dependent, protein–matrix coupling has been shown
to occur in various simple saccharide amorphous matrices, which is stronger in trehalose. The efficiency as bioprotectant
of trehalose has been ascribed to this tight coupling, since the appearance of damages on biological structures will more
involve structural variations of the surrounding matrix. Here we present, as an applicative follow-up of this research line,
a Fourier transform infrared study on protein–matrix coupling in commercial maltodextrins and trehalosyldextrins solid amorphous
systems, with carboxymyoglobin embedded, and compare the results with analogous system containing trehalose and maltose, previously
reported. Results point out that trehalosyldextrins are useful candidates as protecting agents, even though with an efficiency
lower than trehalose, and could be used when the rheological properties of relative long-chain oligosaccharides are needed.
However, it appears that a substantial improvement could be obtained by removal of the small fraction of glucose. 相似文献
996.
997.
Labelle-Dumais C Dilworth DJ Harrington EP de Leau M Lyons D Kabaeva Z Manzini MC Dobyns WB Walsh CA Michele DE Gould DB 《PLoS genetics》2011,7(5):e1002062
Muscle-eye-brain disease (MEB) and Walker Warburg Syndrome (WWS) belong to a spectrum of autosomal recessive diseases characterized by ocular dysgenesis, neuronal migration defects, and congenital muscular dystrophy. Until now, the pathophysiology of MEB/WWS has been attributed to alteration in dystroglycan post-translational modification. Here, we provide evidence that mutations in a gene coding for a major basement membrane protein, collagen IV alpha 1 (COL4A1), are a novel cause of MEB/WWS. Using a combination of histological, molecular, and biochemical approaches, we show that heterozygous Col4a1 mutant mice have ocular dysgenesis, neuronal localization defects, and myopathy characteristic of MEB/WWS. Importantly, we identified putative heterozygous mutations in COL4A1 in two MEB/WWS patients. Both mutations occur within conserved amino acids of the triple-helix-forming domain of the protein, and at least one mutation interferes with secretion of the mutant proteins, resulting instead in intracellular accumulation. Expression and posttranslational modification of dystroglycan is unaltered in Col4a1 mutant mice indicating that COL4A1 mutations represent a distinct pathogenic mechanism underlying MEB/WWS. These findings implicate a novel gene and a novel mechanism in the etiology of MEB/WWS and expand the clinical spectrum of COL4A1-associated disorders. 相似文献
998.
999.
Monti P Perfumo C Bisio A Ciribilli Y Menichini P Russo D Umbach DM Resnick MA Inga A Fronza G 《Molecular cancer research : MCR》2011,9(3):271-279
Germline TP53 mutations result in cancer proneness syndromes known as Li-Fraumeni, Li-Fraumeni-like, and nonsyndromic predisposition with or without family history. To explore genotype/phenotype associations, we previously adopted a functional classification of all germline TP53 mutant alleles based on transactivation. Severe deficiency (SD) alleles were associated with more severe cancer proneness syndromes, and a larger number of tumors, compared with partial deficiency (PD) alleles. Because mutant p53 can exert dominant-negative (DN) effects, we addressed the relationship between DN and clinical manifestations. We reasoned that DN effects might be stronger in familial cancer cases associated with germline TP53 mutations, where mutant alleles coexist with the wild-type allele since conception. We examined 104 p53 mutant alleles with single amino acid substitutions described in the IARC germline database for (i) transactivation capability and (ii) capacity to reduce the activity of the wild-type allele (i.e., DN effect) using a quantitative yeast-based assay. The functional classifications of p53 alleles were then related to clinical variables. We confirmed that a classification based on transactivation alone can identify familial cancer cases with more severe clinical features. Classification based on DN effects allowed us to highlight similar associations but did not reveal distinct clinical subclasses of SD alleles, except for a correlation with tumor tissue prevalence. We conclude that in carriers of germline TP53 mutations transactivation-based classification of TP53 alleles appears more important for genotype/phenotype correlations than DN effects and that haplo-insufficiency of the TP53 gene is an important factor in cancer proneness in humans. 相似文献
1000.