全文获取类型
收费全文 | 512篇 |
免费 | 44篇 |
专业分类
556篇 |
出版年
2024年 | 1篇 |
2023年 | 6篇 |
2022年 | 9篇 |
2021年 | 15篇 |
2020年 | 14篇 |
2019年 | 15篇 |
2018年 | 17篇 |
2017年 | 14篇 |
2016年 | 17篇 |
2015年 | 34篇 |
2014年 | 41篇 |
2013年 | 44篇 |
2012年 | 42篇 |
2011年 | 52篇 |
2010年 | 32篇 |
2009年 | 26篇 |
2008年 | 35篇 |
2007年 | 12篇 |
2006年 | 26篇 |
2005年 | 12篇 |
2004年 | 21篇 |
2003年 | 16篇 |
2002年 | 15篇 |
2001年 | 9篇 |
2000年 | 1篇 |
1999年 | 2篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1974年 | 3篇 |
1957年 | 2篇 |
排序方式: 共有556条查询结果,搜索用时 0 毫秒
81.
Florent Clerc Karli R. Reiding Bas C. Jansen Guinevere S. M. Kammeijer Albert Bondt Manfred Wuhrer 《Glycoconjugate journal》2016,33(3):309-343
Glycosylation is the most abundant and complex protein modification, and can have a profound structural and functional effect on the conjugate. The oligosaccharide fraction is recognized to be involved in multiple biological processes, and to affect proteins physical properties, and has consequentially been labeled a critical quality attribute of biopharmaceuticals. Additionally, due to recent advances in analytical methods and analysis software, glycosylation is targeted in the search for disease biomarkers for early diagnosis and patient stratification. Biofluids such as saliva, serum or plasma are of great use in this regard, as they are easily accessible and can provide relevant glycosylation information. Thus, as the assessment of protein glycosylation is becoming a major element in clinical and biopharmaceutical research, this review aims to convey the current state of knowledge on the N-glycosylation of the major plasma glycoproteins alpha-1-acid glycoprotein, alpha-1-antitrypsin, alpha-1B-glycoprotein, alpha-2-HS-glycoprotein, alpha-2-macroglobulin, antithrombin-III, apolipoprotein B-100, apolipoprotein D, apolipoprotein F, beta-2-glycoprotein 1, ceruloplasmin, fibrinogen, immunoglobulin (Ig) A, IgG, IgM, haptoglobin, hemopexin, histidine-rich glycoprotein, kininogen-1, serotransferrin, vitronectin, and zinc-alpha-2-glycoprotein. In addition, the less abundant immunoglobulins D and E are included because of their major relevance in immunology and biopharmaceutical research. Where available, the glycosylation is described in a site-specific manner. In the discussion, we put the glycosylation of individual proteins into perspective and speculate how the individual proteins may contribute to a total plasma N-glycosylation profile determined at the released glycan level. 相似文献
82.
ISOLATION AND CHARACTERIZATION OF SIX cDNAs INVOLVED IN CARBON METABOLISM IN LAMINARIA DIGITATA (PHAEOPHYCEAE) 总被引:1,自引:0,他引:1
Pascale Moulin Florent Crépineau Bernard Kloareg Catherine Boyen 《Journal of phycology》1999,35(6):1237-1245
An expressed sequence tag (EST) approach was used to retrieve cDNA clones involved in carbon metabolism in Laminaria digitata Lamouroux. Six partial open reading frames were identified, respectively encoding an α-type carbonic anhydrase (CA), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), phosphoglycerate kinase (PGK), glycolate oxidase (GLO), and GDP-4-keto-6-d-mannose-3,5-epimerase-4-reductase, also known as fucose synthase (FS). These enzymes were further characterized through Southern blot analyses, amino acid sequence comparisons, and patterns of expression. In contrast to the other genes, which are expressed in both the gametophytic and sporophytic generations of L. digitata, the α-type carbonic anhydrase messenger RNA was shown by RT-PCR and northern blot analyses to be present in the gametophytes only. The evolutionary relationships of these genes and their interest as molecular tools for investigating carbon fluxes in brown algae are discussed. 相似文献
83.
Juan García-de-Lomas Jordi Sala Violeta Barrios Florent Prunier Antonio Camacho Margarida Machado Miguel Alonso Michael Korn Dani Boix Francisco Hortas Carlos M. García Laura Serrano Gonzalo Muñoz 《Hydrobiologia》2017,787(1):99-110
Aquatic macroinvertebrates in drainage ditches may alter rates of nutrient cycling and decomposition of organic matter but have not been accounted for in studies of ditch biogeochemistry. We collected sediment cores from four pairs of field (intermittent) and collection (perennial) ditches on Maryland’s Eastern Shore monthly from March 2011 to February 2012 to determine how taxonomic and functional group composition varies among different ditch types. We identified 138 taxa and assigned them to functional groups according to trophic position and modes of burrowing. There was no difference in mean abundance of invertebrates (5821 ind./m2) between seasons or types of ditches, and species richness peaked in winter (20 taxa/site) compared to other seasons (15 taxa/site), but did not vary between ditch types. Assemblage composition differed between field and collection ditches, but functional group composition did not. Field ditches flow intermittently which may limit the assemblage to early colonists and taxa adapted to survive desiccation. The benthic macroinvertebrate assemblage was dominated by the collector–gatherer functional feeding group (83.6%) and burrowing taxa (97.1%). Bioturbation by burrowing macroinvertebrates is likely an important process contributing to ecosystem-scale functions of drainage ditches, including regulation of biogeochemical processes occurring at the sediment–water interface. 相似文献
84.
Jordi Sala Stéphanie Gascón David Cunillera-Montcusí Miguel Alonso Francisco Amat Luís Cancela da Fonseca Margarida Cristo Margarita Florencio Juan García-de-Lomas Margarida Machado Maria Rosa Miracle Alexandre Miró José Luis Pérez-Bote Joan Lluís Pretus Florent Prunier Javier Ripoll Juan Rueda María Sahuquillo Laura Serrano Marc Ventura David Verdiell-Cubedo Dani Boix 《Hydrobiologia》2017,784(1):81-91
The deficiency in the distributional data of invertebrate taxa is one of the major impediments acting on the bias towards the low awareness of its conservation status. The present study sets a basic framework to understand the large branchiopods distribution in the Iberian Peninsula and Balearic Islands. Since the extensive surveys performed in the late 1980s, no more studies existed updating the information for the whole studied area. The present study fills the gap, gathering together all available information on large branchiopods distribution since 1995, and analysing the effect of human population density and several landscape characteristics on their distribution, taking into consideration different spatial scales (100 m, 1 km and 10 km). In overall, 28 large branchiopod taxa (17 anostracans, 7 notostracans and 4 spinicaudatans) are known to occur in the area. Approximately 30% of the sites hosted multiple species, with a maximum of 6 species. Significant positive co-occurring species pairs were found clustered together, forming 4 different associations of large branchiopod species. In general, species clustered in the same group showed similar responses to analysed landscape characteristics, usually showing a better fit at higher spatial scales. 相似文献
85.
Reproduction is a complex and energy demanding function. When internal and external conditions might impair reproductive success (negative energy balance, stress, harsh season) reproductive activity has to be repressed. Recent evidence suggests that these inhibitory mechanisms operate on Kiss1-expressing neurons, which were recently shown to be implicated in the regulation of GnRH release. Hamsters are seasonal rodents which are sexually active in long photoperiod and quiescent in short photoperiod. The photoperiodic information is transmitted to the reproductive system by melatonin, a pineal hormone whose secretion is adjusted to night length. The photoperiodic variation in circulating melatonin has been shown to synchronize reproductive activity with seasons, but the mechanisms involved in this effect of melatonin were so far unknown. Recently we have observed that Kiss1 mRNA level in the arcuate nucleus of the Syrian hamster is lower in short photoperiod, when animals are sexually quiescent. Notably, intracerebroventricular infusion of Kiss1 gene product, kisspeptin, in hamsters kept in short photoperiod is able to override the inhibitory photoperiod and to reactivate sexual activity. The inhibition of Kiss1 expression in short photoperiod is driven by melatonin because pinealectomy prevents decrease in Kiss1 mRNA level in short photoperiod and melatonin injection in long photoperiod down regulates Kiss1 expression. Whether melatonin acts directly on arcuate Kiss1 expressing neurons or mediates its action via interneurons is the subject of the current investigations. 相似文献
86.
Lucie Couturier Delphine Taupin Florent Yvergnaux 《Journal of Molecular Catalysis .B, Enzymatic》2009,56(1):29-33
Candida antarctica lipase is well known to convert amines and alcohols into amides and esters. This report describes the development of a solvent-free enzymatic process for the production of fatty alkanolamides. The aminolysis of linoleyl ethyl ester with several aminoalcohols from C2 to C6 (linear or branched compounds), and the very high selectivity of amide compounds have been observed.Our investigation leads us to develop an original biotechnological process for the chemoselective synthesis of new active molecules for cutaneous application. 相似文献
87.
Dana Willner Mike Furlan Matthew Haynes Robert Schmieder Florent E. Angly Joas Silva Sassan Tammadoni Bahador Nosrat Douglas Conrad Forest Rohwer 《PloS one》2009,4(10)
The human respiratory tract is constantly exposed to a wide variety of viruses, microbes and inorganic particulates from environmental air, water and food. Physical characteristics of inhaled particles and airway mucosal immunity determine which viruses and microbes will persist in the airways. Here we present the first metagenomic study of DNA viral communities in the airways of diseased and non-diseased individuals. We obtained sequences from sputum DNA viral communities in 5 individuals with cystic fibrosis (CF) and 5 individuals without the disease. Overall, diversity of viruses in the airways was low, with an average richness of 175 distinct viral genotypes. The majority of viral diversity was uncharacterized. CF phage communities were highly similar to each other, whereas Non-CF individuals had more distinct phage communities, which may reflect organisms in inhaled air. CF eukaryotic viral communities were dominated by a few viruses, including human herpesviruses and retroviruses. Functional metagenomics showed that all Non-CF viromes were similar, and that CF viromes were enriched in aromatic amino acid metabolism. The CF metagenomes occupied two different metabolic states, probably reflecting different disease states. There was one outlying CF virome which was characterized by an over-representation of Guanosine-5′-triphosphate,3′-diphosphate pyrophosphatase, an enzyme involved in the bacterial stringent response. Unique environments like the CF airway can drive functional adaptations, leading to shifts in metabolic profiles. These results have important clinical implications for CF, indicating that therapeutic measures may be more effective if used to change the respiratory environment, as opposed to shifting the taxonomic composition of resident microbiota. 相似文献
88.
Kevin Moreau Sandra Lacas‐Gervais Naonobu Fujita Florent Sebbane Tamotsu Yoshimori Michel Simonet Frank Lafont 《Cellular microbiology》2010,12(8):1108-1123
Yersinia pseudotuberculosis is able to replicate inside macrophages. However, the intracellular trafficking of the pathogen after its entry into the macrophage remains poorly understood. Using in vitro infected bone marrow‐derived macrophages, we show that Y. pseudotuberculosis activates the autophagy pathway. Host cell autophagosomes subverted by bacteria do not become acidified and sustain bacteria replication. Moreover, we report that autophagy inhibition correlated with bacterial trafficking inside an acidic compartment. This study indicates that Y. pseudotuberculosis hijacks the autophagy pathway for its replication and also opens up new opportunities for deciphering the molecular basis of the host cell signalling response to intracellular Yersinia infection. 相似文献
89.
Azoulay M Tuffin G Sallem W Florent JC 《Bioorganic & medicinal chemistry letters》2006,16(12):3147-3149
Many drugs induce severe side-effects caused by their lack of selectivity. One way to overcome this problem is to design a specific system which releases a free drug in a controlled manner. Herein we describe a new way to liberate a drug from a prodrug using the Staudinger ligation as the trigger. 相似文献
90.
Sophie Laget Michael Joulie Florent Le Masson Nobuhiro Sasai Elisabeth Christians Sriharsa Pradhan Richard J. Roberts Pierre-Antoine Defossez 《PloS one》2010,5(8)