全文获取类型
收费全文 | 1543篇 |
免费 | 145篇 |
专业分类
1688篇 |
出版年
2024年 | 3篇 |
2023年 | 13篇 |
2022年 | 47篇 |
2021年 | 81篇 |
2020年 | 50篇 |
2019年 | 66篇 |
2018年 | 69篇 |
2017年 | 50篇 |
2016年 | 74篇 |
2015年 | 116篇 |
2014年 | 114篇 |
2013年 | 123篇 |
2012年 | 138篇 |
2011年 | 135篇 |
2010年 | 73篇 |
2009年 | 55篇 |
2008年 | 91篇 |
2007年 | 75篇 |
2006年 | 50篇 |
2005年 | 52篇 |
2004年 | 50篇 |
2003年 | 38篇 |
2002年 | 36篇 |
2001年 | 5篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 11篇 |
1997年 | 6篇 |
1996年 | 5篇 |
1995年 | 7篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1992年 | 9篇 |
1991年 | 5篇 |
1990年 | 5篇 |
1989年 | 2篇 |
1987年 | 1篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1979年 | 2篇 |
1977年 | 2篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1971年 | 1篇 |
排序方式: 共有1688条查询结果,搜索用时 15 毫秒
991.
Gian Luigi Sottocasa Giulia Baldini Gabriella Sandri Giancarlo Lunazzi Claudio Tiribelli 《生物化学与生物物理学报:生物膜》1982,685(2):123-128
Liposomes containing 150 mM KCl and 0.48 mM sulfobromophthalein have been prepared. The internal pH was set at 6.5, a value at which sulfobromopthalein is colorless. When brought to alkaline pH a certain amount of the dye is deprotonated and can be read spectrophotometrically as external sulfobromophthalein. Upon addition of Triton X-100 the membrane is dissolved and all sulfobromophthalein present in the preparation may be measured. Addition of bilitranslocase to such a preparation of liposomes causes the internal sulfobromophthalein to leave the internal compartment. The rate of this phenomenon may be followed directly and shown to be greatly accelerated by the addition of valinomycin. The latter finding indicates that sulfobromophthalein transport occurs in response to a membrane diffusion potential created by permeabilisation to K+ of liposomes brought about by valinomycin (uniport). The permeability change induced by bilitranslocase is specific and does not reflect an alteration of the normal impermeability of liposomes to small ions such as protons or Ca2+. 相似文献
992.
993.
994.
995.
Antonella Virgilio Veronica Esposito Annalisa Pecoraro Annapina Russo Valentina Vellecco Antonietta Pepe Mariarosaria Bucci Giulia Russo Aldo Galeone 《Nucleic acids research》2020,48(22):12556
The thrombin binding aptamer (TBA) possesses promising antiproliferative properties. However, its development as an anticancer agent is drastically impaired by its concomitant anticoagulant activity. Therefore, suitable chemical modifications in the TBA sequence would be required in order to preserve its antiproliferative over anticoagulant activity. In this paper, we report structural investigations, based on circular dichroism (CD) and nuclear magnetic resonance spectroscopy (NMR), and biological evaluation of four pairs of enantiomeric heterochiral TBA analogues. The four TBA derivatives of the d-series are composed by d-residues except for one l-thymidine in the small TT loops, while their four enantiomers are composed by l-residues except for one d-thymidine in the same TT loop region. Apart from the left-handedness for the l-series TBA derivatives, CD and NMR measurements have shown that all TBA analogues are able to adopt the antiparallel, monomolecular, ‘chair-like’ G-quadruplex structure characteristic of the natural D-TBA. However, although all eight TBA derivatives are endowed with remarkable cytotoxic activities against colon and lung cancer cell lines, only TBA derivatives of the l-series show no anticoagulant activity and are considerably resistant in biological environments. 相似文献
996.
Barbara Pelosi Marta Pratelli Sara Migliarini Giulia Pacini Massimo Pasqualetti 《PloS one》2015,10(8)
Serotonin has been gaining increasing attention during the last two decades due to the dual function of this monoamine as key regulator during critical developmental events and as neurotransmitter. Importantly, unbalanced serotonergic levels during critical temporal phases might contribute to the onset of neuropsychiatric disorders, such as schizophrenia and autism. Despite increasing evidences from both animal models and human genetic studies have underpinned the importance of serotonin homeostasis maintenance during central nervous system development and adulthood, the precise role of this molecule in time-specific activities is only beginning to be elucidated. Serotonin synthesis is a 2-step process, the first step of which is mediated by the rate-limiting activity of Tph enzymes, belonging to the family of aromatic amino acid hydroxylases and existing in two isoforms, Tph1 and Tph2, responsible for the production of peripheral and brain serotonin, respectively. In the present study, we generated and validated a conditional knockout mouse line, Tph2
flox/flox, in which brain serotonin can be effectively ablated with time specificity. We demonstrated that the Cre-mediated excision of the third exon of Tph2 gene results in the production of a Tph2
null allele in which we observed the near-complete loss of brain serotonin, as well as the growth defects and perinatal lethality observed in serotonin conventional knockouts. We also revealed that in mice harbouring the Tph2
null allele, but not in wild-types, two distinct Tph2 mRNA isoforms are present, namely Tph2Δ3 and Tph2Δ3Δ4, with the latter showing an in-frame deletion of amino acids 84–178 and coding a protein that could potentially retain non-negligible enzymatic activity. As we could not detect Tph1 expression in the raphe, we made the hypothesis that the Tph2Δ3Δ4 isoform can be at the origin of the residual, sub-threshold amount of serotonin detected in the brain of Tph2
null/null mice. Finally, we set up a tamoxifen administration protocol that allows an efficient, time-specific inactivation of brain serotonin synthesis. On the whole, we generated a suitable genetic tool to investigate how serotonin depletion impacts on time-specific events during central nervous system development and adulthood life. 相似文献
997.
998.
Paola Laiolo Javier Seoane Juan Carlos Illera Giulia Bastianelli Luis María Carrascal José Ramón Obeso 《Proceedings. Biological sciences / The Royal Society》2015,282(1821)
The fit between life histories and ecological niche is a paradigm of phenotypic evolution, also widely used to explain patterns of species co-occurrence. By analysing the lifestyles of a sympatric avian assemblage, we show that species'' solutions to environmental problems are not unbound. We identify a life-history continuum structured on the cost of reproduction along a temperature gradient, as well as habitat-driven parental behaviour. However, environmental fit and trait convergence are limited by niche filling and by within-species variability of niche traits, which is greater than variability of life histories. Phylogeny, allometry and trade-offs are other important constraints: lifetime reproductive investment is tightly bound to body size, and the optimal allocation to reproduction for a given size is not established by niche characteristics but by trade-offs with survival. Life histories thus keep pace with habitat and climate, but under the limitations imposed by metabolism, trade-offs among traits and species'' realized niche. 相似文献
999.
Daniela Chessa Giulia Ganau Luisella Spiga Antonio Bulla Vittorio Mazzarello Gian Vittorio Campus Salvatore Rubino 《PloS one》2016,11(1)
Staphylococcus epidermidis and Staphylococcus aureus are currently considered two of the most important pathogens in nosocomial infections associated with catheters and other medical implants and are also the main contaminants of medical instruments. However because these species of Staphylococcus are part of the normal bacterial flora of human skin and mucosal surfaces, it is difficult to discern when a microbial isolate is the cause of infection or is detected on samples as a consequence of contamination. Rapid identification of invasive strains of Staphylococcus infections is crucial for correctly diagnosing and treating infections. The aim of the present study was to identify specific genes to distinguish between invasive and contaminating S. epidermidis and S. aureus strains isolated on medical devices; the majority of our samples were collected from breast prostheses. As a first step, we compared the adhesion ability of these samples with their efficacy in forming biofilms; second, we explored whether it is possible to determine if isolated pathogens were more virulent compared with international controls. In addition, this work may provide additional information on these pathogens, which are traditionally considered harmful bacteria in humans, and may increase our knowledge of virulence factors for these types of infections. 相似文献
1000.
Federica Del Chierico Pamela Vernocchi Andrea Petrucca Paola Paci Susana Fuentes Giulia Praticò Giorgio Capuani Andrea Masotti Sofia Reddel Alessandra Russo Cristina Vallone Guglielmo Salvatori Elsa Buffone Fabrizio Signore Giuliano Rigon Andrea Dotta Alfredo Miccheli Willem M. de Vos Bruno Dallapiccola Lorenza Putignani 《PloS one》2015,10(9)
The colonization and development of gut microbiota immediately after birth is highly variable and depends on several factors, such as delivery mode and modality of feeding during the first months of life. A cohort of 31 mother and neonate pairs, including 25 at-term caesarean (CS) and 6 vaginally (V) delivered neonates (DNs), were included in this study and 121 meconium/faecal samples were collected at days 1 through 30 following birth. Operational taxonomic units (OTUs) were assessed in 69 stool samples by phylogenetic microarray HITChip and inter- and intra-individual distributions were established by inter-OTUs correlation matrices and OTUs co-occurrence or co-exclusion networks. 1H-NMR metabolites were determined in 70 stool samples, PCA analysis was performed on 55 CS DNs samples, and metabolome/OTUs co-correlations were assessed in 45 CS samples, providing an integrated map of the early microbiota OTUs-metabolome. A microbiota “core” of OTUs was identified that was independent of delivery mode and lactation stage, suggesting highly specialized communities that act as seminal colonizers of microbial networks. Correlations among OTUs, metabolites, and OTUs-metabolites revealed metabolic profiles associated with early microbial ecological dynamics, maturation of milk components, and host physiology. 相似文献