全文获取类型
收费全文 | 592篇 |
免费 | 48篇 |
出版年
2023年 | 3篇 |
2022年 | 5篇 |
2021年 | 7篇 |
2020年 | 10篇 |
2019年 | 10篇 |
2018年 | 11篇 |
2017年 | 12篇 |
2016年 | 25篇 |
2015年 | 31篇 |
2014年 | 29篇 |
2013年 | 40篇 |
2012年 | 50篇 |
2011年 | 50篇 |
2010年 | 27篇 |
2009年 | 14篇 |
2008年 | 42篇 |
2007年 | 37篇 |
2006年 | 20篇 |
2005年 | 27篇 |
2004年 | 36篇 |
2003年 | 25篇 |
2002年 | 33篇 |
2001年 | 2篇 |
2000年 | 6篇 |
1999年 | 9篇 |
1998年 | 11篇 |
1997年 | 8篇 |
1995年 | 3篇 |
1994年 | 5篇 |
1993年 | 5篇 |
1992年 | 3篇 |
1991年 | 4篇 |
1990年 | 6篇 |
1989年 | 3篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 4篇 |
1983年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1970年 | 1篇 |
1967年 | 1篇 |
1966年 | 2篇 |
1961年 | 1篇 |
排序方式: 共有640条查询结果,搜索用时 15 毫秒
511.
Elena McCarthy David Moretti Len Thomas Nancy DiMarzio Ronald Morrissey Susan Jarvis Jessica Ward Annamaria Izzi Ashley Dilley 《Marine Mammal Science》2011,27(3):E206-E226
The number and distribution of vocalizing groups of Blainville's beaked whales (Mesoplodon densirostris) were analyzed before, during, and after multiship mid‐frequency active sonar operations at the US Navy's Atlantic Undersea Test and Evaluation Center (AUTEC) in the Bahamas. Groups of foraging animals were isolated by detecting their echolocation clicks using an array of bottom‐mounted hydrophones. Two data sets were evaluated consisting of 115 and 240 h of acoustic data in May 2007 and 2008, respectively. Vocal activity was observed to decline during active sonar exercises and increase upon cessation of sonar transmissions in both data sets. Vocal activity did not recover to preexposure levels in the postexposure time period in 2007 nor in the initial postexposure period in the 2008 data set. Clicks detected during sonar operations were generally found to be on the periphery of the hydrophone field and vocal durations declined for those groups that remained on the range in that time period. Receive levels were calculated for several vocal groups of whales and indicated that animals continued to forage when exposed to sonar at levels as high as 157 dB re: μPa. 相似文献
512.
Bacilieri M Naggi A Ceol M Schleicher ED Tosetto E Comoli M Torri G Moro S Palumbo M Gambaro G 《Glycobiology》2011,21(8):1029-1037
A number of glycosaminoglycan (GAG) species related to heparin, dermatan sulfate (DeS) and chondroitin sulfate were tested for their ability to interfere with the physiological expression and/or pathological overexpression of the TGF-β1 gene. The influence of the molecular weight, molecular weight distribution, degree of sulfation and location of the sulfate groups was examined in an attempt to unveil fine relationships between structure and activity. The nature of the polysaccharide plays a major part, heparins proving able to inhibit both basal and stimulated TGF-β1 gene expression, DeSs being essentially inactive and chondroitin sulfates only inhibiting stimulated TGF-β1 gene expression. Within this frame, the particular physical and chemical properties of some GAGs appear to further modulate TGF-β1 gene response. Judging from our investigation, chondroitin sulfates seem the most promising for potential pharmacological applications in disorders characterized by fibrogenic TGF-β1 overexpression. 相似文献
513.
This study determined emm subtypes of Streptococcus pyogenes strains isolated from asymptomatic carriers and children with pharyngitis. All strains were previously investigated for fibronectin-binding genes (prtF1 and prtF2) and antimicrobial susceptibility. The most significant differences between the two groups, which share only 5 of the 14 detected emmsubtypes, concern the presence of the two more common emmsubtypes, 12.0 (50.0% vs. 3.1%, for asymptomatic carriers and children with pharyngitis, respectively) and 1.0 (28.1% vs. 0%, for children with pharyngitis and asymptomatic carriers, respectively). 相似文献
514.
515.
Daniela Rossi Annamaria Marra Pietro Picconi Massimo Serra Laura Catenacci Milena Sorrenti Erik Laurini Maurizio Fermeglia Sabrina Pricl Stefania Brambilla Nicoletta Almirante Marco Peviani Daniela Curti Simona Collina 《Bioorganic & medicinal chemistry》2013,21(9):2577-2586
Strong pharmacological evidences indicate that σ1 receptors are implicated in the pathophysiology of all major CNS disorders. In the last years our research group has conducted extensive studies aimed at discovering novel σ1 ligands and we recently selected (R/S)-RC-33 as a novel potent and selective σ1 receptor agonist. As continuation of our work in this field, here we report our efforts in the development of this new σ1 receptor agonist. Initially, we investigated the binding of (R) and (S) enantiomers of RC-33 to the σ1 receptor by in silico experiments. The close values of the predicted affinity of (R)-RC-33 and (S)-RC-33 for the protein evidenced the non-stereoselective binding of RC-33 to the σ1 receptor; this, in turn, supported further development and characterization of RC-33 in its racemic form. Subsequently, we set-up a scaled-up, optimized synthesis of (R/S)-RC-33 along with some compound characterization data (e.g., solubility in different media and solid state characterization by thermal analysis techniques). Finally, metabolic studies of RC-33 in different biological matrices (e.g., plasma, blood, and hepatic S9 fraction) of different species (e.g., rat, mouse, dog, and human) were performed. (R/S)-RC-33 is generally stable in all examined biological matrices, with the only exception of rat and human liver S9 fractions in the presence of NADPH. In such conditions, the compound is subjected to a relevant oxidative metabolism, with a degradation of approximately 65% in rat and 69% in human.Taken together, our results demonstrated that (R/S)-RC-33 is a highly potent, selective, metabolically stable σ1 agonist, a promising novel neuroprotective drug candidate. 相似文献
516.
Riassunto È stato preso in esame, mediante analisi pollinologiche di depositi torbosi, il rimboschimento postglaciale della parte meridionale della venezia Tridentina per le quote da 1000 a 1400 m. I risultati hanno permesso di stabilire che nel versante meridionale del sistema alpino l'Abete, in determinate posizioni, ha partecipato in modo considerevole — spesso imponente — alla constituzione delle foreste dopo il periodo dei Pini, fino al periodo del Faggio. Il comportamento della sua espansione è risultato analogo a quello già descritto per il versante settentrionale; ciò vien messo in evidenza mediante un grafico the mostra schematicamente l'aspetto forestale dei due versanti nel periodo Querceto-Picea-Abies del posglaciale. 相似文献
517.
Targeted therapy of human glioblastoma via delivery of a toxin through a peptide directed to cell surface nucleolin
下载免费PDF全文
![点击此处可从《Journal of cellular physiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Anne‐Chloé Dhez Elisabetta Benedetti Andrea Antonosante Gloria Panella Brigida Ranieri Tiziana M. Florio Loredana Cristiano Francesco Angelucci Francesco Giansanti Luana Di Leandro Michele d'Angelo Marina Melone Antonella De Cola Luca Federici Renato Galzio Ilaria Cascone Fabio Raineri Annamaria Cimini José Courty Antonio Giordano Rodolfo Ippoliti 《Journal of cellular physiology》2018,233(5):4091-4105
518.
Gniewomir Latacz Annamaria Lubelska Magdalena Jastrzębska-Więsek Anna Partyka Katarzyna Kucwaj-Brysz Anna Wesołowska Katarzyna Kieć-Kononowicz Jadwiga Handzlik 《Bioorganic & medicinal chemistry letters》2018,28(5):878-883
We report the in vitro drug-likeness studies and in vivo pharmacological evaluation for a new potent 5-HT7 receptor antagonist MF-8 (5-(4-fluorophenyl)-3-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)-5-methylhydantoin). The in vitro tests showed good permeability, very good metabolic stability, low risk of drug-drug interactions and satisfying safety profile. Moreover, MF-8 showed excellent antidepressant-like activity in the forced swim test in rodents and promising anxiolytic-like activity in the four-plate test in mice. Regarding the potent affinity, high selectivity and antagonistic activity of MF-8 for the 5-HT7 receptor as well as excellent drug – like properties in vitro and confirmed in vivo pharmacological activity, MF-8 should be considered as a very significant molecule in the search for a new class of anti-depressant drugs. 相似文献
519.
Annamaria Sandomenico Annalia Focà Luca Sanguigno Andrea Caporale Giuseppina Focà Angelica Pignalosa 《MABS-AUSTIN》2016,8(8):1575-1589
Post-translational modifications (PTMs) strongly influence the structure and function of proteins. Lysine side chain acetylation is one of the most widespread PTMs, and it plays a major role in several physiological and pathological mechanisms. Protein acetylation may be detected by mass spectrometry (MS), but the use of monoclonal antibodies (mAbs) is a useful and cheaper option. Here, we explored the feasibility of generating mAbs against single or multiple acetylations within the context of a specific sequence. As a model, we used the unstructured N-terminal domain of APE1, which is acetylated on Lys27, Lys31, Lys32 and Lys35. As immunogen, we used a peptide mixture containing all combinations of single or multi-acetylated variants encompassing the 24–39 protein region. Targeted screening of the resulting clones yielded mAbs that bind with high affinity to only the acetylated APE1 peptides and the acetylated protein. No binding was seen with the non-acetylated variant or unrelated acetylated peptides and proteins, suggesting a high specificity for the APE1 acetylated molecules. MAbs could not finely discriminate between the differently acetylated variants; however, they specifically bound the acetylated protein in mammalian cell extracts and in intact cells and tissue slices from both breast cancers and from a patient affected by idiopathic dilated cardiomyopathy. The data suggest that our approach is a rapid and cost-effective method to generate mAbs against specific proteins modified by multiple acetylations or other PTMs. 相似文献
520.
Marianthi Karali Maria Persico Margherita Mutarelli Annamaria Carissimo Mariateresa Pizzo Veer Singh?Marwah Concetta Ambrosio Michele Pinelli Diego Carrella Stefano Ferrari Diego Ponzin Vincenzo Nigro Diego di?Bernardo Sandro Banfi 《Nucleic acids research》2016,44(4):1525-1540
MicroRNAs play a fundamental role in retinal development and function. To characterise the miRNome of the human retina, we carried out deep sequencing analysis on sixteen individuals. We established the catalogue of retina-expressed miRNAs, determined their relative abundance and found that a small number of miRNAs accounts for almost 90% of the retina miRNome. We discovered more than 3000 miRNA variants (isomiRs), encompassing a wide range of sequence variations, which include seed modifications that are predicted to have an impact on miRNA action. We demonstrated that a seed-modifying isomiR of the retina-enriched miR-124-3p was endowed with different targeting properties with respect to the corresponding canonical form. Moreover, we identified 51 putative novel, retina-specific miRNAs and experimentally validated the expression for nine of them. Finally, a parallel analysis of the human Retinal Pigment Epithelium (RPE)/choroid, two tissues that are known to be crucial for retina homeostasis, yielded notably distinct miRNA enrichment patterns compared to the retina. The generated data are accessible through an ad hoc database. This study is the first to reveal the complexity of the human retina miRNome at nucleotide resolution and constitutes a unique resource to assess the contribution of miRNAs to the pathophysiology of the human retina. 相似文献