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971.
Manuja Kaluarachchi Claire L. Boulangé Ibrahim Karaman John C. Lindon Timothy M. D. Ebbels Paul Elliott Russell P. Tracy Nels C. Olson 《Metabolomics : Official journal of the Metabolomic Society》2018,14(3):32
Introduction
Differences in the metabolite profiles between serum and plasma are incompletely understood.Objectives
To evaluate metabolic profile differences between serum and plasma and among plasma sample subtypes.Methods
We analyzed serum, platelet rich plasma (PRP), platelet poor plasma (PPP), and platelet free plasma (PFP), collected from 8 non-fasting apparently healthy women, using untargeted standard 1D and CPMG 1H NMR and reverse phase and hydrophilic (HILIC) UPLC-MS. Differences between metabolic profiles were evaluated using validated principal component and orthogonal partial least squares discriminant analysis.Results
Explorative analysis showed the main source of variation among samples was due to inter-individual differences with no grouping by sample type. After correcting for inter-individual differences, lipoproteins, lipids in VLDL/LDL, lactate, glutamine, and glucose were found to discriminate serum from plasma in NMR analyses. In UPLC-MS analyses, lysophosphatidylethanolamine (lysoPE)(18:0) and lysophosphatidic acid(20:0) were higher in serum, and phosphatidylcholines (PC)(16:1/18:2, 20:3/18:0, O-20:0/22:4), lysoPC(16:0), PE(O-18:2/20:4), sphingomyelin(18:0/22:0), and linoleic acid were lower. In plasma subtype analyses, isoleucine, leucine, valine, phenylalanine, glutamate, and pyruvate were higher among PRP samples compared with PPP and PFP by NMR while lipids in VLDL/LDL, citrate, and glutamine were lower. By UPLC-MS, PE(18:0/18:2) and PC(P-16:0/20:4) were higher in PRP compared with PFP samples.Conclusions
Correction for inter-individual variation was required to detect metabolite differences between serum and plasma. Our results suggest the potential importance of inter-individual effects and sample type on the results from serum and plasma metabolic phenotyping studies.972.
The Auxin-Regulated CrRLK1L Kinase ERULUS Controls Cell Wall Composition during Root Hair Tip Growth 总被引:1,自引:0,他引:1
Sébastjen Schoenaers Daria Balcerowicz Gordon Breen Kristine Hill Malgorzata Zdanio Grégory Mouille Tara J. Holman Jaesung Oh Michael H. Wilson Natalia Nikonorova Lam Dai Vu Ive De Smet Ranjan Swarup Winnok H. De Vos Isabel Pintelon Dirk Adriaensen Claire Grierson Malcolm J. Bennett Kris Vissenberg 《Current biology : CB》2018,28(5):722-732.e6
973.
Jean-François Fournier Yushma Bhurruth-Alcor Branislav Musicki Jérome Aubert Michèle Aurelly Claire Bouix-Peter Karinne Bouquet Laurent Chantalat Marion Delorme Bénédicte Drean Gwenaelle Duvert Nicolas Fleury-Bregeot Blanche Gauthier Karine Grisendi Craig S. Harris Laurent F. Hennequin Tatiana Isabet Florence Joly Loïc Tomas 《Bioorganic & medicinal chemistry letters》2018,28(17):2985-2992
A series of squaramide-based hydroxamic acids were designed, synthesized and evaluated against human HDAC enzyme. Squaramides were found to be potent in the Hut78 cell line, but initially suffered from low solubility. Leads with improved solubility and metabolic profiles were shown to be class I, IIB and IV selective. 相似文献
974.
Gilles Ouvry Franck Bihl Claire Bouix-Peter Olivier Christin Claire Defoin-Platel Sophie Deret Christophe Feret David Froude Feriel Hacini-Rachinel Craig S. Harris Catherine Hervouet Guillaume Lafitte Anne-Pascale Luzy Branislav Musicki Danielle Orfila Veronique Parnet Coralie Pascau Jonathan Pascau Laurent F. Hennequin 《Bioorganic & medicinal chemistry letters》2018,28(8):1269-1273
Progress in the identification of suitable RORγ inverse agonists as clinical candidates has been hampered by the high lipophilicity that seems required for high potency on this nuclear receptor. In this context, we decided to focus on the replacement of the hydroxymethyl group found on known modulators to determine if more polarity could be tolerated in this position. SAR of the replacement of this moiety is presented in this article leading to the identification of sulfoximine derivatives as potent modulators with pharmacological activity in the in vivo mouse Imiquimod psoriasis model. 相似文献
975.
Mark Bell David Foley Claire Naylor Colin Robinson Jennifer Riley Ola Epemolu Paul Scullion Yoko Shishikura Elad Katz W.H. Irwin McLean Paul Wyatt Kevin D. Read Andrew Woodland 《Bioorganic & medicinal chemistry letters》2018,28(19):3255-3259
The oral S1PR1 agonist ponesimod demonstrated substantial efficacy in a phase II clinical trial of psoriasis. Unfortunately, systemic side effects were observed, which included lymphopenia and transient bradycardia. We sought to develop a topical soft-drug S1PR1 agonist with an improved therapeutic index. By modifying ponesimod, we discovered an ester series of S1PR agonists. To increase metabolic instability in plasma we synthesised esters described as specific substrates for paraoxonase and butyrylcholinesterases, esterases present in human plasma. 相似文献
976.
Etienne Thoreau Jean-Marie Arlabosse Claire Bouix-Peter Sandrine Chambon Laurent Chantalat Sébastien Daver Laurence Dumais Gwenaëlle Duvert Angélique Feret Gilles Ouvry Jonathan Pascau Catherine Raffin Nicolas Rodeville Catherine Soulet Samuel Tabet Sandrine Talano Thibaud Portal 《Bioorganic & medicinal chemistry letters》2018,28(10):1736-1741
Retinoids have a dominant role in topical acne therapy and to date, only RARβ and RARγ dual agonists have reached the market. Given the tissue distribution of RAR isoforms, it was hypothesized that developing RARγ -selective agonists could yield a new generation of topical acne treatments that would increase safety margins while maintaining the robust efficacy of previous drugs. Structural knowledge derived from the X-ray structure of known γ-selective CD437, suggested the design of a novel triaryl series of agonists which was optimized and ultimately led to the discovery of Trifarotene/CD5789. 相似文献
977.
Vincent Battesti Muriel Gros-Balthazard Clémence Ogéron Sarah Ivorra Jean-Frédéric Terral Claire Newton 《Human ecology: an interdisciplinary journal》2018,46(4):529-546
We evaluate date palm (Phoenix dactylifera L.) agrobiodiversity of Siwa oasis, Egypt, located at the crossroads of ancient Trans-Saharan routes, focusing on diversity both as expressed and maintained by the folk categorization system of Siwa inhabitants (through an ethnographic analysis) and as described by genetic sciences and a morphometric tool based on size and geometry of seeds. We verified that some named types are true cultivars, sharing not only a formal identity, important for Isiwan people, but also a genetic identity. However, we also confirm the existence of “ethnovarieties,” i.e., voluntary collections of multiple clones sharing phenotypic characteristics with the same local name, suggesting the genetic richness is higher than the apparent agrobiodiversity estimated by a superficial ethnobotanical approach. Finally, our research offers new insights on the relative importance of feral and cultivated date palms. 相似文献
978.
Stuhr Marleen Meyer Achim Reymond Claire E. Narayan Gita R. Rieder Vera Rahnenführer Jörg Kucera Michal Westphal Hildegard Muhando Christopher A. Hallock Pamela 《Coral reefs (Online)》2018,37(3):811-824
Coral Reefs - Adaptation, acclimatization and symbiont diversity are known to regulate thermal tolerance in corals, but the role of these mechanisms remains poorly constrained in other... 相似文献
979.