全文获取类型
收费全文 | 4756篇 |
免费 | 327篇 |
国内免费 | 5篇 |
专业分类
5088篇 |
出版年
2024年 | 3篇 |
2023年 | 40篇 |
2022年 | 79篇 |
2021年 | 156篇 |
2020年 | 87篇 |
2019年 | 114篇 |
2018年 | 167篇 |
2017年 | 116篇 |
2016年 | 187篇 |
2015年 | 269篇 |
2014年 | 286篇 |
2013年 | 347篇 |
2012年 | 435篇 |
2011年 | 466篇 |
2010年 | 286篇 |
2009年 | 227篇 |
2008年 | 260篇 |
2007年 | 331篇 |
2006年 | 253篇 |
2005年 | 230篇 |
2004年 | 219篇 |
2003年 | 186篇 |
2002年 | 152篇 |
2001年 | 34篇 |
2000年 | 16篇 |
1999年 | 14篇 |
1998年 | 28篇 |
1997年 | 18篇 |
1996年 | 18篇 |
1995年 | 6篇 |
1994年 | 10篇 |
1993年 | 7篇 |
1991年 | 4篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1974年 | 3篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1968年 | 1篇 |
1966年 | 1篇 |
1964年 | 1篇 |
排序方式: 共有5088条查询结果,搜索用时 15 毫秒
991.
992.
Micha Turek Katarzyna Banasiak Magorzata Piechota Nilesh Shanmugam Matylda Macias Magorzata Alicja
liwiska Marta Niklewicz Konrad Kowalski Natalia Nowak Agnieszka Chacinska Wojciech Pokrzywa 《EMBO reports》2021,22(8)
Caenorhabditis elegans body wall muscles release vesicles called exophers that transport muscle‐synthesized yolk proteins to nourish the next generation. 相似文献
993.
Bunney TD Harris R Gandarillas NL Josephs MB Roe SM Sorli SC Paterson HF Rodrigues-Lima F Esposito D Ponting CP Gierschik P Pearl LH Driscoll PC Katan M 《Molecular cell》2006,21(4):495-507
Ras proteins signal to a number of distinct pathways by interacting with diverse effectors. Studies of ras/effector interactions have focused on three classes, Raf kinases, ral guanylnucleotide-exchange factors, and phosphatidylinositol-3-kinases. Here we describe ras interactions with another effector, the recently identified phospholipase C epsilon (PLCepsilon). We solved structures of PLCepsilon RA domains (RA1 and RA2) by NMR and the structure of the RA2/ras complex by X-ray crystallography. Although the similarity between ubiquitin-like folds of RA1 and RA2 proves that they are homologs, only RA2 can bind ras. Some of the features of the RA2/ras interface are unique to PLCepsilon, while the ability to make contacts with both switch I and II regions of ras is shared only with phosphatidylinositol-3-kinase. Studies of PLCepsilon regulation suggest that, in a cellular context, the RA2 domain, in a mode specific to PLCepsilon, has a role in membrane targeting with further regulatory impact on PLC activity. 相似文献
994.
Cadavid Isabel Cristina Giraldo Carlos E. Balbinott Natalia González Mailyn Adriana Uribe Sandra Inés de Boer Hugo J. 《Journal of plant biochemistry and biotechnology.》2022,31(4):938-952
Journal of Plant Biochemistry and Biotechnology - Solanum is the largest and most diverse genus of the Solanaceae family. The genus includes around 1,400 species, and almost a third belong to... 相似文献
995.
Antagonistic regulation of alpha-actinin alternative splicing by CELF proteins and polypyrimidine tract binding protein 总被引:6,自引:0,他引:6
The alpha-actinin gene has a pair of alternatively spliced exons. The smooth muscle (SM) exon is repressed in most cell types by polypyrimidine tract binding protein (PTB). CELF (CUG-BP and ETR3-like factors) family proteins, splicing regulators whose activities are altered in myotonic dystrophy, were found to coordinately regulate selection of the two alpha-actinin exons. CUG-BP and ETR3 activated the SM exon, and along with CELF4 they were also able to repress splicing of the NM (nonmuscle) exon both in vivo and in vitro. Activation of SM exon splicing was associated with displacement of PTB from the polypyrimidine tract by binding of CUG-BP at adjacent sites. Our data provides direct evidence for the activity of CELF proteins as both activators and repressors of splicing within a single-model system of alternative splicing, and suggests a model whereby alpha-actinin alternative splicing is regulated by synergistic and antagonistic interactions between members of the CELF and PTB families. 相似文献
996.
Tatiana V. Burova Irina A. Golubeva Natalia V. Grinberg Alexander Ya. Mashkevich Valery Ya. Grinberg Anatoly I. Usov Luciano Navarini Attilio Cesro 《Biopolymers》1996,39(4):517-529
Thermally induced order-disorder conformational transition in succinoglycan was studied using the method of high-sensitivity differential scanning microcalorimetry within the range of polysaccharide concentrations from 0.1 to 3.5 mg mL−1 at NaCl concentrations 0, 0.01, and 0.1M. The positions and shapes of the excess heat capacity curves depended substantially on both the NaCl and polysaccharide concentrations. At low polysaccharide concentrations in salt-free solution the experimental curves were closely approximated by the two-state model suggesting the transition mechanism to be of the single helix-coil type. With increasing polysaccharide and/or NaCl concentration, the experimental curves changed significantly in symmetry, which indicated a changing transition mechanism. At high polysaccharide concentrations or in the presence of the salt, the order-disorder transition of succinoglycan was shown to include two stages: the cooperative dissociation of the helix dimer and subsequent two-state melting of the helix monomer. The dependence of thermodynamic parameters for the dissociation and melting of helix structures in succinoglycan on NaCl and polysaccharide concentrations was obtained by fitting the experimental excess heat capacity curves. The cooperativity parameter σ for the single helix-coil transition as well as the average length of the helix segment of succinoglycan were calculated. Some features of succinoglycan ordering in solution are discussed. © 1996 John Wiley & Sons, Inc. 相似文献
997.
Villar-Pique A de Groot NS Sabaté R Acebrón SP Celaya G Fernàndez-Busquets X Muga A Ventura S 《Journal of molecular biology》2012,421(2-3):270-281
The formation of aggregates by misfolded proteins is thought to be inherently toxic, affecting cell fitness. This observation has led to the suggestion that selection against protein aggregation might be a major constraint on protein evolution. The precise fitness cost associated with protein aggregation has been traditionally difficult to evaluate. Moreover, it is not known if the detrimental effect of aggregates on cell physiology is generic or depends on the specific structural features of the protein deposit. In bacteria, the accumulation of intracellular protein aggregates reduces cell reproductive ability, promoting cellular aging. Here, we exploit the cell division defects promoted by the intracellular aggregation of Alzheimer's-disease-related amyloid β peptide in bacteria to demonstrate that the fitness cost associated with protein misfolding and aggregation is connected to the protein sequence, which controls both the in vivo aggregation rates and the conformational properties of the aggregates. We also show that the deleterious impact of protein aggregation on bacterial division can be buffered by molecular chaperones, likely broadening the sequential space on which natural selection can act. Overall, the results in the present work have potential implications for the evolution of proteins and provide a robust system to experimentally model and quantify the impact of protein aggregation on cell fitness. 相似文献
998.
Aleksei G. Menzorov Konstantin E. Orishchenko Veniamin S. Fishman Anastasia A. Shevtsova Roman V. Mungalov Inna E. Pristyazhnyuk Elena A. Kizilova Natalia M. Matveeva Natalia Alenina Michael Bader Nikolai B. Rubtsov Oleg L. Serov 《Journal of cellular biochemistry》2019,120(10):17208-17218
Neuronal tracing is a modern technology that is based on the expression of fluorescent proteins under the control of cell type–specific promoters. However, random genomic integration of the reporter construct often leads to incorrect spatial and temporal expression of the marker protein. Targeted integration (or knock-in) of the reporter coding sequence is supposed to provide better expression control by exploiting endogenous regulatory elements. Here we describe the generation of two fluorescent reporter systems: enhanced green fluorescent protein (EGFP) under pan-neural marker class III β-tubulin (Tubb3) promoter and mEos2 under serotonergic neuron-specific tryptophan hydroxylase 2 (Tph2) promoter. Differentiation of Tubb3-EGFP embryonic stem (ES) cells into neurons revealed that though Tubb3-positive cells express EGFP, its expression level is not sufficient for the neuronal tracing by routine fluorescent microscopy. Similarly, the expression levels of mEos2-TPH2 in differentiated ES cells was very low and could be detected only on messenger RNA level using polymerase chain reaction-based methods. Our data shows that the use of endogenous regulatory elements to control transgene expression is not always beneficial compared with the random genomic integration. 相似文献
999.
Natalia L. Duarte Stephen Colagiuri Taniela Palu Xing Li Wang David E.L. Wilcken 《Obesity (Silver Spring, Md.)》2003,11(4):512-517
We compared the current prevalence of increased BMI and type 2 diabetes in a representative group of Tongan subjects with measurements made in 1973, and we determined the distribution and possible interrelations with the UCP2 insertion/deletion (ins/del) polymorphism of these variables. We documented the BMI, glucose tolerance, and standard lipid variables in 1012 Tongan subjects (429 men and 583 women, ages 15 to 85 years) during 1998 and 2000 and compared the BMI findings with those of the 1973 survey. We also genotyped for the UCP2 ins/del polymorphism, assessed its association with obesity and type 2 diabetes, and compared its prevalence with those reported for other ethnic populations. The mean BMI ± SD was greatly increased in both men (30.2 ± 5.4 kg/m2) and women (33.8 ± 6.2 kg/m2), representing increases since 1973 of 11.9% and 19.4%, respectively. The genotype frequencies were 97% for the del/del genotype and 3% for the ins/del genotype; we found no ins/ins homozygotes. This distribution is strikingly different from those reported for white, South Indian, Pima Native‐American, and Asian populations (49 to 77% for del/del genotype). We conclude that there is a marked prevalence of obesity in Tonga, a prevalence that has increased since 1973. We also conclude that there is a unique, near‐uniform distribution of the UCP2 45‐bp ins/del polymorphism in Tongans. This may be the result of a founder effect and may be relevant to the prevalence of obesity and type 2 diabetes in Tonga. 相似文献
1000.