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911.
Gene delivery by lentivirus vectors 总被引:13,自引:0,他引:13
The capacity to efficiently transduce nondividing cells, shuttle large genetic payloads, and maintain stable long-term transgene
expression are attributes that have brought lentiviral vectors to the forefront of gene delivery vehicles for research and
therapeutic applications in a clinical setting. Our discussion initiates with advances in lentiviral vector development and
how these sophisticated lentiviral vectors reflect improvements in safety, regarding the prevention of replication competent
lentiviruses (RCLs), vector mobilization, and insertional mutagenesis. Additionally, we describe conventional molecular regulatory
systems to manage gene expression levels in a spatial and temporal fashion in the context of a lentiviral vector. State of
the art technology for lentiviral vector production by transient transfection and packaging cell lines are explicitly presented
with current practices used for concentration, purification, titering, and determining the safety of a vector stock. We summarize
lentiviral vector applications that have received a great deal of attention in recent years including the generation of transgenic
animals and the stable delivery of RNA interference molecules. Concluding remarks address some of the successes in preclinical
animals, and the recent transition of lentiviral vectors to human clinical trials as therapy for a variety of infectious and
genetic diseases. 相似文献
912.
Alpi A Amrhein N Bertl A Blatt MR Blumwald E Cervone F Dainty J De Michelis MI Epstein E Galston AW Goldsmith MH Hawes C Hell R Hetherington A Hofte H Juergens G Leaver CJ Moroni A Murphy A Oparka K Perata P Quader H Rausch T Ritzenthaler C Rivetta A Robinson DG Sanders D Scheres B Schumacher K Sentenac H Slayman CL Soave C Somerville C Taiz L Thiel G Wagner R 《Trends in plant science》2007,12(4):135-136
913.
PrepMS: TOF MS data graphical preprocessing tool 总被引:1,自引:0,他引:1
Karpievitch YV Hill EG Smolka AJ Morris JS Coombes KR Baggerly KA Almeida JS 《Bioinformatics (Oxford, England)》2007,23(2):264-265
We introduce a simple-to-use graphical tool that enables researchers to easily prepare time-of-flight mass spectrometry data for analysis. For ease of use, the graphical executable provides default parameter settings, experimentally determined to work well in most situations. These values, if desired, can be changed by the user. PrepMS is a stand-alone application made freely available (open source), and is under the General Public License (GPL). Its graphical user interface, default parameter settings, and display plots allow PrepMS to be used effectively for data preprocessing, peak detection and visual data quality assessment. AVAILABILITY: Stand-alone executable files and Matlab toolbox are available for download at: http://sourceforge.net/projects/prepms 相似文献
914.
MOTIVATION: Due to advances in experimental technologies, such as microarray, mass spectrometry and nuclear magnetic resonance, it is feasible to obtain large-scale data sets, in which measurements for a large number of features can be simultaneously collected. However, the sample sizes of these data sets are usually small due to their relatively high costs, which leads to the issue of concordance among different data sets collected for the same study: features should have consistent behavior in different data sets. There is a lack of rigorous statistical methods for evaluating this concordance or discordance. METHODS: Based on a three-component normal-mixture model, we propose two likelihood ratio tests for evaluating the concordance and discordance between two large-scale data sets with two sample groups. The parameter estimation is achieved through the expectation-maximization (E-M) algorithm. A normal-distribution-quantile-based method is used for data transformation. RESULTS: To evaluate the proposed tests, we conducted some simulation studies, which suggested their satisfactory performances. As applications, the proposed tests were applied to three SELDI-MS data sets with replicates. One data set has replicates from different platforms and the other two have replicates from the same platform. We found that data generated by SELDI-MS showed satisfactory concordance between replicates from the same platform but unsatisfactory concordance between replicates from different platforms. AVAILABILITY: The R codes are freely available at http://home.gwu.edu/~ylai/research/Concordance. 相似文献
915.
916.
Ritchie AJ Whittall C Lazenby JJ Chhabra SR Pritchard DI Cooley MA 《Immunology and cell biology》2007,85(8):596-602
The Pseudomonas aeruginosa quorum-sensing signal molecule N-3-oxododecanoyl)-L-homoserine lactone (OdDHL) has been reported to affect the function of a wide range of mammalian cell types, including cells of the immune system. In T cells, it has been reported to inhibit the production of most cytokines, and it has been reported to inhibit the function of antigen-presenting cells. The intracellular target of OdDHL in these cells remains to be identified, although the lipophilic nature of the molecule suggested that the target could be membrane associated. We explored the association of radiolabelled OdDHL with the membrane and cytoplasm of Jurkat T-cell lines and of primary murine T cells and dendritic cells. We found that not only did 3H-OdDHL enter the cytoplasm of Jurkat cells without disproportionate association with the cell membrane, it also reached maximum levels in the cytoplasm very quickly, and that the intracellular concentration was proportional to the extracellular concentration. Similar results were obtained when 3H-OdDHL was incubated with primary murine T cells or cultured dendritic cells. In addition, we show that the cellular distribution of OdDHL does not significantly alter after stimulation of Jurkat cells or primary murine CD4 T cells with immobilized anti-CD3, with little activity being associated with nuclear fractions. Together, these data strongly suggest that OdDHL enters mammalian cells by passive mechanisms, and that it does not preferentially associate with the membrane or nucleus upon T-cell receptor ligation. 相似文献
917.
Gardner S Maudsley S Millar RP Pawson AJ 《Molecular endocrinology (Baltimore, Md.)》2007,21(12):3028-3038
918.
919.
Through bioinformatics and experimental approaches, we have assigned the first biochemical property to a predicted protein product in the human genome as a new 14-3-3 binding protein. 14-3-3 client proteins represent a diverse group of regulatory molecules that often function as signaling integrators in response to various environmental cues and include proteins such as Bad and Foxo. Using 14-3-3 as a probe in a yeast two-hybrid screen, we identified a novel 14-3-3 binding protein with unknown function, initially designated as clone 546. Confocal microscopy revealed that clone 546 localized to the nucleus of mammalian cells. Additional studies show that the gene encoding clone 546 is expressed in many human tissues, including the thymus, as well as a number of cancer cell lines. The interaction of clone 546 with 14-3-3 was confirmed in mammalian cells. Interestingly, this interaction was markedly enhanced by the expression of activated Akt/PKB, suggesting a phosphorylation dependent event. Mutational analysis was carried out to identify Ser479 as the predominant residue that mediates the clone 546/14-3-3 association. Phosphorylation of Ser479 by AKT/PKB further supports a critical role for Akt/PKB in regulation of the clone 546/14-3-3 interaction. On the basis of these findings, we named this undefined protein FAKTS: Fourteen-three-three associated AKT Substrate. 相似文献
920.
Crystal structure of a transcription regulator (TM1602) from Thermotoga maritima at 2.3 A resolution
Weekes D Miller MD Krishna SS McMullan D McPhillips TM Acosta C Canaves JM Elsliger MA Floyd R Grzechnik SK Jaroszewski L Klock HE Koesema E Kovarik JS Kreusch A Morse AT Quijano K Spraggon G van den Bedem H Wolf G Hodgson KO Wooley J Deacon AM Godzik A Lesley SA Wilson IA 《Proteins》2007,67(1):247-252