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Traumatic brain injury (TBI) is associated with significant infectious and inflammatory complications. Though increasing evidence suggests that rFVIIa administration may be efficacious for the pre-hospital treatment of TBI, the FVIIa-tissue factor complex has been shown to be immunologically active. To date the cytokine response to rFVIIa administration for the treatment of TBI has not been evaluated. Twenty anesthetized immature Yorkshire swine underwent fluid percussion TBI. At 15 min following injury, animals were randomized to receive either 90 μg/kg rFVIIa (rFVIIa) or nothing. Animals were observed for 6 h and then euthanized. Plasma and cerebrospinal (CSF) samples were collected at 0 min and 360 min, and ELISA analysis of TNF-α, IL-1β and IL-10 was performed. Survival in both groups was 100%. Baseline cytokine concentrations were not statistically different between rFVIIa and control animals in plasma or CSF. Animals in both groups did not have significant changes in plasma cytokine concentrations following TBI. Control animals did not demonstrate significant changes from baseline of CSF cytokine concentrations following TBI. The administration of rFVIIa however, resulted in significant increases in CSF TNF-α concentration (232.0 pg/ml ± 75.9 vs 36.4 pg/ml ± 10.4, p = 0.036) and IL-10 concentration (10.7 pg/ml ± 0.6 vs 8.8 pg/ml ± 0.1, p = 0.015). IL-1β concentrations were not significantly changed over the experimental time course. These results suggest that rFVIIa administration for the treatment of TBI is not immunologically inert, and is associated with increased CSF concentrations of TNF-α and IL-10. 相似文献
144.
Behnke A Engel M Christen R Nebel M Klein RR Stoeck T 《Environmental microbiology》2011,13(2):340-349
Initial environmental pyrosequencing studies suggested highly complex protistan communities with phylotype richness decisively higher than previously estimated. However, recent studies on individual bacteria or artificial bacterial communities evidenced that pyrosequencing errors may skew our view of the true complexity of microbial communities. We pyrosequenced two diversity markers (hypervariable regions V4 and V9 of the small-subunit rDNA) of an intertidal protistan model community, using the Roche GS-FLX and the most recent GS-FLX Titanium sequencing systems. After pyrosequencing 24 reference sequences we obtained up to 2039 unique tags (from 3879 V4 GS-FLX Titanium reads), 77% of which were singletons. Even binning sequences that share 97% similarity still emulated a pseudodiversity exceeding the true complexity of the model community up to three times (V9 GS-FLX). Pyrosequencing error rates were higher for V4 fragments compared with the V9 domain and for the GS-FLX Titanium compared with the GS-FLX system. Furthermore, this experiment revealed that error rates are taxon-specific. As an outcome of this study we suggest a fast and efficient strategy to discriminate pyrosequencing signals from noise in order to more realistically depict the structure of protistan communities using simple tools that are implemented in standard tag data-processing pipelines. 相似文献
145.
Stalling of replication forks at lesions is a serious threat to genomic integrity and cell viability. Cells have developed a variety of pathways that allow continuation of synthesis, including translesion synthesis, postreplication repair and homologous recombination. We have devised a sensitive genetic system for detection of sister chromatid interactions in Saccharomyces cerevisiae. A 266bp sequence duplication in the KanMX4 module was generated and reversions were scored via G418 resistant colonies. Both 4-NQO induced and spontaneous reversions are strictly dependent on RAD52. Damage-induced reversions are also largely dependent on RAD51. Thus, most damage-induced events require a strand invasion step. Induced reversions were not affected in rev3 mutants and partially reduced in rad30 mutants indicating an involvement of Pol η. In cells lacking Mph1, a member of the FANCM family of DNA helicases, that has been implicated in a pathway for fork reactivation involving homologous recombination, damage-induced events are significantly reduced. Together with the spontaneous mutator phenotype of mph1 mutants this data strongly suggest that Mph1 has an additional function in recombination besides its previously described ability to disrupt D-loops. We propose that Mph1 promotes D-loop formation. 相似文献
146.
Improved phylogenetic resolution of toxic and non-toxic Alexandrium strains using a concatenated rDNA approach 总被引:1,自引:0,他引:1
Russell J.S. Orr Anke Stüken Thomas Rundberget Wenche Eikrem Kjetill S. Jakobsen 《Harmful algae》2011,10(6):676-688
Dinoflagellates of the genus Alexandrium are known producers of paralytic shellfish toxins. Species within the genus have similar phenotypes making morphological identification problematical. The use of Alexandrium rDNA sequence data is therefore increasing, resulting in the improved resolution of evolutionary relationships by phylogenetic inferences. However, the true branching pattern within Alexandrium remains unresolved, with minimal support shown for the main phylogentic branch. The aim of this study is to improve phylogenetic resolution via a concatenated rDNA approach with a broad sample of taxa, allowing inference of the evolutionary pattern between species and toxins. 27 Alexandrium strains from 10 species were tested with HPLC for PSP toxin presence and additionally sequenced for 18S, ITS1, 5.8S, ITS2 and 28S rDNA before being phylogenetically inferred together with all available orthologous sequences from NCBI. The resulting alignment is the largest to date for the genus, in terms of both inferred characters and taxa, thus allowing for the improved phylogenetic resolution of evolutionary patterns there in. No phylogenetic pattern between PSP producing and non-producing strains could be established, however the terminal tamarense complex was shown to produce more PSP analogues than basal clades. Additionally, we distinguish a high number of polymorphic regions between the two copies of A. fundyense rDNA, thus allowing us to demonstrate the presence of chimeric sequences within GenBank, as well as a possible over estimation of diversification within the tamarense complex. 相似文献
147.
Anke Teichler Rebecca Eckardt Stephanie Hoeppener Christian Friebe Jolke Perelaer Alessia Senes Mauro Morana Christoph J. Brabec Ulrich S. Schubert 《Liver Transplantation》2011,1(1):105-114
Polymer:fullerene blends were screened in a combinatorial approach using inkjet printing thin film libraries for photovoltaic devices. The application of inkjet printing enabled a fast and simple experimental workflow from film preparation to the study of structure‐property‐relationships with a very high material efficiency. Inkjet printing requires less material for the preparation of thin film libraries in comparison to other dispensing techniques, like spin‐coating. Two polymers (PCPDTBT, PSBTBT) and two fullerene derivatives (mono‐PCBM, bis‐PCBM) were investigated in various blend ratios, concentrations, solvent ratios, and film thicknesses. Morphological and optical properties of the inkjet printed films were investigated and compared with spin‐coated films. This study shows the principle of an experimental setup from solution preparation to film characterization for the combinatorial investigation of large polymer:fullerene libraries. 相似文献
148.
Reinhold D Bank U Entz D Goihl A Stoye D Wrenger S Brocke S Thielitz A Stefin S Nordhoff K Heimburg A Täger M Ansorge S 《Biological chemistry》2011,392(3):233-237
Cellular dipeptidyl peptidase IV (DP IV, CD26) and amino-peptidase N (APN, CD13) play regulatory roles in T cell activation and represent potential targets for treatment of inflammatory disorders. We have developed a novel therapeutic strategy, 'peptidase-targeted Immunoregulation' (PETIR?), which simultaneously targets both cellular DP IV and APN via selective binding sites different from the active sites with a single inhibitor. To prove the therapeutic concept of PETIR? in autoimmunity of the central nervous system (CNS), we evaluated the effect of a single substance, PETIR-001, in an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) in SJL/J mice. Administration of PETIR-001 significantly delayed and decreased clinical signs of active EAE, when given in a therapeutic manner intraperitoneally from day 15 to day 24 after induction of EAE. Both the acute phase and the first relapse of EAE were markedly inhibited. Importantly, a similar therapeutic benefit was obtained after oral administration of PETIR-001 from day 12 to day 21 after disease induction. Our results demonstrate that PETIR-001 exhibits a therapeutic effect on EAE in SJL/J mice. Thus, PETIR? represents a novel and efficient therapeutic approach for immunotherapy of CNS inflammation. 相似文献
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Roodenburg AJ Schlatmann A Dötsch-Klerk M Daamen R Dong J Guarro M Stergiou M Sayed N Ronoh E Jansen L Seidell JC 《PloS one》2011,6(2):e14721