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151.
Clarke B Demont E Dingwall C Dunsdon R Faller A Hawkins J Hussain I MacPherson D Maile G Matico R Milner P Mosley J Naylor A O'Brien A Redshaw S Riddell D Rowland P Soleil V Smith KJ Stanway S Stemp G Sweitzer S Theobald P Vesey D Walter DS Ward J Wayne G 《Bioorganic & medicinal chemistry letters》2008,18(3):1011-1016
Inhibition of the aspartyl protease BACE-1 has the potential to deliver a disease-modifying therapy for Alzheimer's disease. Herein, is described the lead generation effort which resulted, with the support of X-ray crystallography, in the discovery of potent inhibitors based on a hydroxy ethylamine (HEA) transition-state mimetic. These inhibitors were capable of lowering amyloid production in a cell-based assay. 相似文献
152.
Salim Bourras Kaitlin Elyse McNally Roi Ben-David Francis Parlange Stefan Roffler Coraline Rosalie Praz Simone Oberhaensli Fabrizio Menardo Daniel Stirnweis Zeev Frenkel Luisa Katharina Schaefer Simon Flückiger Georges Treier Gerhard Herren Abraham B. Korol Thomas Wicker Beat Keller 《The Plant cell》2015,27(10):2991-3012
In cereals, several mildew resistance genes occur as large allelic series; for example, in wheat (Triticum aestivum and Triticum turgidum), 17 functional Pm3 alleles confer agronomically important race-specific resistance to powdery mildew (Blumeria graminis). The molecular basis of race specificity has been characterized in wheat, but little is known about the corresponding avirulence genes in powdery mildew. Here, we dissected the genetics of avirulence for six Pm3 alleles and found that three major Avr loci affect avirulence, with a common locus_1 involved in all AvrPm3-Pm3 interactions. We cloned the effector gene AvrPm3a2/f2 from locus_2, which is recognized by the Pm3a and Pm3f alleles. Induction of a Pm3 allele-dependent hypersensitive response in transient assays in Nicotiana benthamiana and in wheat demonstrated specificity. Gene expression analysis of Bcg1 (encoded by locus_1) and AvrPm3 a2/f2 revealed significant differences between isolates, indicating that in addition to protein polymorphisms, expression levels play a role in avirulence. We propose a model for race specificity involving three components: an allele-specific avirulence effector, a resistance gene allele, and a pathogen-encoded suppressor of avirulence. Thus, whereas a genetically simple allelic series controls specificity in the plant host, recognition on the pathogen side is more complex, allowing flexible evolutionary responses and adaptation to resistance genes. 相似文献
153.
Thomas A. Morton Donald B. Bennett Edward R. Appelbaum Donna M. Cusimano Kyung O. Johanson Rosalie E. Matico Peter R. Young Michael Doyle Irwin M. Chaiken 《Journal of molecular recognition : JMR》1994,7(1):47-55
A surface plasmon resonance (SPR) biosensor was used to study the interaction of human interleukin-5 (hIL5) with its receptor. IL5 is a major growth factor in the production and activation of eosinophilis. The receptor for IL5 is composed of two subunits, α and β. The α subunit provides the specificity for IL5 and consist of an extracellular soluble domain, a single transmembrane region and a cytoplasmic tail. We expressed the soluble domain of the human IL5 receptor α subunit (shIL5Rα) and human IL5 (hIL5) in Drosophila. Both hIL5 and shIL5Rα were immobilized separately through amine groups onto the carboxylated dextran layer of sensor chips of the BIAcore? (Pharmacia) SPR biosensor after N-hydroxysuccinimide/carbodiimide activation of the chip surface. Interactions were measured for the complementary macromolecule, either shIL5Rα or hIL5, in solution. Kinetics of binding of soluble analyst to immobilized ligand were measured and from this the association rate constant, dissociation rate constant and equilibrium dissociation constant (Kd) were derived. With immobilized shIL5Rα and soluble hIL5, the measured Kd was 2 nM . A similar value was obtained by titration calorimetry. The Kd for Drosophila expressed receptor and IL5 is higher than the values reported for proteins expressed in different systems, likely due to differences in the methods of interaction analysis used for differences in protein glycosylation. Receptor-IL5 binding was relatively pH independent between pH 6.5 and 9.5. Outside this range the dissociation rate increased with compressibility little increased in association rate. The values obtained for the interaction of hIL5 and shIL5Rα were found to depend on which component was immobilized; the Kd was 5.5 nM with immobilized hIL5 and soluble shIL5Rα. The SPR biosensor provides a unified methodology to measure the interaction properties of shIL5Rα and hIL5 derivatives, mutants and mimetic as well as to evaluate potential antagonists of the receptor-cytokine interaction. 相似文献
154.
155.
Dekker Erik Zijp Michiel C. van de Kamp Mirjam E. Temme Elisabeth H. M. van Zelm Rosalie 《The International Journal of Life Cycle Assessment》2020,25(12):2315-2324
The International Journal of Life Cycle Assessment - Recently, an update of the Life Cycle Impact Assessment (LCIA) method ReCiPe was released: ReCiPe 2016. The aim of this study was to analyse the... 相似文献
156.
Anna Kounina Manuele Margni Jean-Baptiste Bayart Anne-Marie Boulay Markus Berger Cecile Bulle Rolf Frischknecht Annette Koehler Llorenç Milà i Canals Masaharu Motoshita Montserrat Núñez Gregory Peters Stephan Pfister Brad Ridoutt Rosalie van Zelm Francesca Verones Sebastien Humbert 《The International Journal of Life Cycle Assessment》2013,18(3):707-721
157.
Rosalie Wunderlich 《Plant Systematics and Evolution》1959,106(3-4):203-293
Ohne ZusammenfassungEs ist mir ein Bedürfnis, auch an dieser Stelle Herrn Professor Dr. L.Geitler meinen aufrichtigsten Dank auszusprechen. Nur durch sein großzügiges, verständnisvolles Entgegenkommen, seine ständige Ermutigung und Förderung war die Durchführung dieser Arbeit überhaupt möglich.Großen Dank schulde ich ferner Herrn Prof. P.Maheshwari (Delhi) für die Beschaffung zahlreicher indischer Literatur und Frau Dr. H.Nietsch (Wien) für das mühevolle Durchlesen des Manuskriptes und viele wertvolle Kritik. 相似文献
158.
159.
Nanja A. C. Van Geel Ilse G. Mollet Sofie De Schepper Esther P. M. Tjin Karim Vermaelen Rachael A. Clark Thomas S. Kupper Rosalie M. Luiten Jo Lambert 《Pigment cell & melanoma research》2010,23(3):375-384
Segmental vitiligo is often ascribed to the neurogenic theory of melanocyte destruction, although data about the initial etiopathological events are scarce. Clinical, histopathological and T-cell phenotypic analyses were performed during the early onset of a segmental vitiligo lesion in a patient with associated halo nevi. Histopathological analysis revealed a lymphocytic infiltrate, mainly composed of CD8+ T-cells and some CD4+ T-cells around the dermo–epidermal junction. Flow cytometry analysis of resident T-cells revealed a clear enrichment of pro-inflammatory IFN-γ producing CD8+ T-cells in lesional skin compared to the non-lesional skin. Using human leukocyte antigen-peptide tetramers (MART-1, tyrosinase, gp100), increased numbers of T cells, recognizing melanocyte antigens were found in segmental vitiligo lesional skin, as compared with the non-lesional skin and the blood. Our findings indicate that a CD8+ melanocyte specific T cell-mediated immune response, as observed in generalized vitiligo, also plays a role in segmental vitiligo with associated halo nevi. 相似文献
160.
Hyunju Ryu XiaoXin Sun Yingxiao Chen Yanping Li Xiaoyan Wang Roselyn S Dai HongMing Zhu John Klimek Larry David Lev M Fedorov Yoshiaki Azuma Rosalie C Sears MuShui Dai 《EMBO reports》2021,22(6)
SUMOylation plays a crucial role in regulating diverse cellular processes including ribosome biogenesis. Proteomic analyses and experimental evidence showed that a number of nucleolar proteins involved in ribosome biogenesis are modified by SUMO. However, how these proteins are SUMOylated in cells is less understood. Here, we report that USP36, a nucleolar deubiquitinating enzyme (DUB), promotes nucleolar SUMOylation. Overexpression of USP36 enhances nucleolar SUMOylation, whereas its knockdown or genetic deletion reduces the levels of SUMOylation. USP36 interacts with SUMO2 and Ubc9 and directly mediates SUMOylation in cells and in vitro. We show that USP36 promotes the SUMOylation of the small nucleolar ribonucleoprotein (snoRNP) components Nop58 and Nhp2 in cells and in vitro and their binding to snoRNAs. It also promotes the SUMOylation of snoRNP components Nop56 and DKC1. Functionally, we show that knockdown of USP36 markedly impairs rRNA processing and translation. Thus, USP36 promotes snoRNP group SUMOylation and is critical for ribosome biogenesis and protein translation. 相似文献