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991.
Werner Sandmann 《Mathematical biosciences》2009,221(1):43-2141
Stochastic simulation of biological systems proceeds by repeatedly generating sample paths or trajectories of the underlying stochastic process, from which many relevant and important system properties can be obtained. While a great deal of research is targeted towards accelerated trajectory generation, issues concerned with the variability across trajectories are often neglected. Advanced methods for properly quantifying the statistical accuracy and determining a reasonable number of trajectories are hardly addressed formally in the context of biological system simulation, though mathematical statistics provides a large body of powerful theory. We invoke this theory and show how mathematically well-founded sequential estimation approaches serve for systematically generating enough but not too many trajectories for achieving a certain prescribed accuracy. The practical applicability is demonstrated and illustrated by numerical examples through simulation studies of an immigration-death process and a gene regulatory network. 相似文献
992.
Stefan Kirsch Juanjo Pasantes Andreas Wolf Nadia Bogdanova Claudia Münch Arseni Markoff Petra Pennekamp Michael Krawczak Bernd Dworniczak Werner Schempp 《BMC evolutionary biology》2009,9(1):14-1
Correction to Kirsch S, Pasantes J, Wolf A, Bogdanova N, Münch C, Pennekamp P, Krawczak M, Dworniczak B, Schempp W: Chromosomal evolution of the
PKD1
gene family in primates. BMC Evolutionary Biology 2008, 8 :263 (doi:10.1186/1471-2148-8-263) 相似文献
993.
Antonio Cabrera Alex Kozik Werner Howad Pere Arus Amy F Iezzoni Esther van der Knaap 《BMC genomics》2009,10(1):562
Background
Detailed comparative genome analyses within the economically important Rosaceae family have not been conducted. This is largely due to the lack of conserved gene-based molecular markers that are transferable among the important crop genera within the family [e.g. Malus (apple), Fragaria (strawberry), and Prunus (peach, cherry, apricot and almond)]. The lack of molecular markers and comparative whole genome sequence analysis for this family severely hampers crop improvement efforts as well as QTL confirmation and validation studies.Results
We identified a set of 3,818 rosaceaous unigenes comprised of two or more ESTs that correspond to single copy Arabidopsis genes. From this Rosaceae Conserved Orthologous Set (RosCOS), 1039 were selected from which 857 were used for the development of intron-flanking primers and allele amplification. This led to successful amplification and subsequent mapping of 613 RosCOS onto the Prunus TxE reference map resulting in a genome-wide coverage of 0.67 to 1.06 gene-based markers per cM per linkage group. Furthermore, the RosCOS primers showed amplification success rates from 23 to 100% across the family indicating that a substantial part of the RosCOS primers can be directly employed in other less studied rosaceaous crops. Comparisons of the genetic map positions of the RosCOS with the physical locations of the orthologs in the Populus trichocarpa genome identified regions of colinearity between the genomes of Prunus-Rosaceae and Populus-Salicaceae.Conclusion
Conserved orthologous genes are extremely useful for the analysis of genome evolution among closely and distantly related species. The results presented in this study demonstrate the considerable potential of the mapped Prunus RosCOS for genome-wide marker employment and comparative whole genome studies within the Rosaceae family. Moreover, these markers will also function as useful anchor points for the genome sequencing efforts currently ongoing in this family as well as for comparative QTL analyses.994.
Michele Abate Karin Gravare Silbernagel Carl Siljeholm Angelo Di Iorio Daniele De Amicis Vincenzo Salini Suzanne Werner Roberto Paganelli 《Arthritis research & therapy》2009,11(3):235-15
The intrinsic pathogenetic mechanisms of tendinopathies are largely unknown and whether inflammation or degeneration has the
prominent role is still a matter of debate. Assuming that there is a continuum from physiology to pathology, overuse may be
considered as the initial disease factor; in this context, microruptures of tendon fibers occur and several molecules are
expressed, some of which promote the healing process, while others, including inflammatory cytokines, act as disease mediators.
Neural in-growth that accompanies the neovessels explains the occurrence of pain and triggers neurogenic-mediated inflammation.
It is conceivable that inflammation and degeneration are not mutually exclusive, but work together in the pathogenesis of
tendinopathies. 相似文献
995.
The human Y chromosome carries four human Y-chromosomal euchromatin/heterochromatin transition regions, all of which are characterized by the presence of interchromosomal segmental duplications. The Yq11.1/Yq11.21 transition region harbours a peculiar segment composed of an imperfectly organized tandem-repeat structure encoding four members of the double homeobox (DUX) gene family. By comparative fluorescence in situ hybridization (FISH) analysis we have documented the primary appearance of Y-chromosomal DUX genes (DUXY) on the gibbon Y chromosome. The major amplification and dispersal of DUXY paralogs occurred after the gibbon and hominid lineages had diverged. Orthologous DUXY loci of human and chimpanzee show a highly similar structural organization. Sequence alignment survey, phylogenetic reconstruction and recombination detection analyses of human and chimpanzee DUXY genes revealed the existence of all copies in a common ancestor. Comparative analysis of the circumjacent beta-satellites indicated that DUXY genes and beta-satellites evolved in concert. However, evolutionary forces acting on DUXY genes may have induced amino acid sequence differences in the orthologous chimpanzee and human DUXY open reading frames (ORFs). The acquisition of complete ORFs in human copies might relate to evolutionary advantageous functions indicating neo-functionalization. We propose an evolutionary scenario in which an ancestral tandem array DUX gene cassette transposed to the hominoid Y chromosome followed by lineage-specific chromosomal rearrangements paved the way for a species-specific evolution of the Y-chromosomal members of a large highly diverged homeobox gene family. 相似文献
996.
Jan Rupp Lisa Pfleiderer Christiane Jugert Sonja Moeller Matthias Klinger Klaus Dalhoff Werner Solbach Steffen Stenger Tamas Laskay Ger van Zandbergen 《PloS one》2009,4(6)
Background
Intracellular pathogens have developed elaborate strategies for silent infection of preferred host cells. Chlamydia pneumoniae is a common pathogen in acute infections of the respiratory tract (e.g. pneumonia) and associated with chronic lung sequelae in adults and children. Within the lung, alveolar macrophages and polymorph nuclear neutrophils (PMN) are the first line of defense against bacteria, but also preferred host phagocytes of chlamydiae.Methodology/Principal Findings
We could show that C. pneumoniae easily infect and hide inside neutrophil granulocytes until these cells become apoptotic and are subsequently taken up by macrophages. C. pneumoniae infection of macrophages via apoptotic PMN results in enhanced replicative activity of chlamydiae when compared to direct infection of macrophages, which results in persistence of the pathogen. Inhibition of the apoptotic recognition of C. pneumoniae infected PMN using PS- masking Annexin A5 significantly lowered the transmission of chlamydial infection to macrophages. Transfer of apoptotic C. pneumoniae infected PMN to macrophages resulted in an increased TGF-ß production, whereas direct infection of macrophages with chlamydiae was characterized by an enhanced TNF-α response.Conclusions/Significance
Taken together, our data suggest that C. pneumoniae uses neutrophil granulocytes to be silently taken up by long-lived macrophages, which allows for efficient propagation and immune protection within the human host. 相似文献997.
Correction: Caldendrin–Jacob: A Protein Liaison That Couples NMDA Receptor Signalling to the Nucleus
Daniela C Dieterich Anna Karpova Marina Mikhaylova Irina Zdobnova Imbritt K?nig Marco Landwehr Martin Kreutz Karl-Heinz Smalla Karin Richter Peter Landgraf Carsten Reissner Tobias M Boeckers Werner Zuschratter Christina Spilker Constanze I Seidenbecher Craig C Garner Eckart D Gundelfinger Michael R Kreutz 《PLoS biology》2009,7(1)
998.
Daniel Rittirsch Michael A. Flierl Danielle E. Day Brian A. Nadeau Firas S. Zetoune J. Vidya Sarma Clement M. Werner Guido A. Wanner Hans-Peter Simmen Markus S. Huber-Lang Peter A. Ward 《PLoS pathogens》2009,5(6)
Pathogen-pattern-recognition by Toll-like receptors (TLRs) and pathogen clearance after immune complex formation via engagement with Fc receptors (FcRs) represent central mechanisms that trigger the immune and inflammatory responses. In the present study, a linkage between TLR4 and FcγR was evaluated in vitro and in vivo. Most strikingly, in vitro activation of phagocytes by IgG immune complexes (IgGIC) resulted in an association of TLR4 with FcγRIII (CD16) based on co-immunoprecipitation analyses. Neutrophils and macrophages from TLR4 mutant (mut) mice were unresponsive to either lipopolysaccharide (LPS) or IgGIC in vitro, as determined by cytokine production. This phenomenon was accompanied by the inability to phosphorylate tyrosine residues within immunoreceptor tyrosine-based activation motifs (ITAMs) of the FcRγ-subunit. To transfer these findings in vivo, two different models of acute lung injury (ALI) induced by intratracheal administration of either LPS or IgGIC were employed. As expected, LPS-induced ALI was abolished in TLR4 mut and TLR4−/− mice. Unexpectedly, TLR4 mut and TLR4−/− mice were also resistant to development of ALI following IgGIC deposition in the lungs. In conclusion, our findings suggest that TLR4 and FcγRIII pathways are structurally and functionally connected at the receptor level and that TLR4 is indispensable for FcγRIII signaling via FcRγ-subunit activation. 相似文献
999.
Heiko F. Stahl Tanja Fauti Nina Ullrich Tobias Bopp Jan Kubach Werner Rust Paul Labhart Vassili Alexiadis Christian Becker Mathias Hafner Andreas Weith Martin C. Lenter Helmut Jonuleit Edgar Schmitt Detlev Mennerich 《PloS one》2009,4(9)
Background
In humans and mice naturally occurring CD4+CD25+ regulatory T cells (nTregs) are a thymus-derived subset of T cells, crucial for the maintenance of peripheral tolerance by controlling not only potentially autoreactive T cells but virtually all cells of the adaptive and innate immune system. Recent work using Dicer-deficient mice irrevocably demonstrated the importance of miRNAs for nTreg cell-mediated tolerance.Principal Findings
DNA-Microarray analyses of human as well as murine conventional CD4+ Th cells and nTregs revealed a strong up-regulation of mature miR-155 (microRNA-155) upon activation in both populations. Studying miR-155 expression in FoxP3-deficient scurfy mice and performing FoxP3 ChIP-Seq experiments using activated human T lymphocytes, we show that the expression and maturation of miR-155 seem to be not necessarily regulated by FoxP3. In order to address the functional relevance of elevated miR-155 levels, we transfected miR-155 inhibitors or mature miR-155 RNAs into freshly-isolated human and mouse primary CD4+ Th cells and nTregs and investigated the resulting phenotype in nTreg suppression assays. Whereas miR-155 inhibition in conventional CD4+ Th cells strengthened nTreg cell-mediated suppression, overexpression of mature miR-155 rendered these cells unresponsive to nTreg cell-mediated suppression.Conclusion
Investigation of FoxP3 downstream targets, certainly of bound and regulated miRNAs revealed the associated function between the master regulator FoxP3 and miRNAs as regulators itself. miR-155 is shown to be crucially involved in nTreg cell mediated tolerance by regulating the susceptibility of conventional human as well as murine CD4+ Th cells to nTreg cell-mediated suppression. 相似文献1000.
Maria E. Teves Hector A. Guidobaldi Diego R. U?ates Raul Sanchez Werner Miska Stephen J. Publicover Aduén A. Morales Garcia Laura C. Giojalas 《PloS one》2009,4(12)
Sperm chemotaxis is a chemical guiding mechanism that may orient spermatozoa to the egg surface. A picomolar concentration gradient of Progesterone (P), the main steroidal component secreted by the cumulus cells that surround the egg, attracts human spermatozoa. In order to elucidate the molecular mechanism of sperm chemotaxis mediated by P, we combine the application of different strategies: pharmacological inhibition of signaling molecules, measurements of the concentrations of second messengers and activation of the chemotactic signaling. Our data implicate a number of classic signal transduction pathways in the response and provide a model for the sequence of events, where the tmAC-cAMP-PKA pathway is activated first, followed by protein tyrosine phosphorylation (equatorial band and flagellum) and calcium mobilization (through IP3R and SOC channels), whereas the sGC-cGMP-PKG cascade, is activated later. These events lead to sperm orientation towards the source of the chemoattractant. The finding proposes a molecular mechanism which contributes to the understanding of the signal transduction pathway that takes place in a physiological process as chemotaxis. 相似文献