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61.
Beena Punnamoottil Carl Herrmann Salvatore D'Aniello Altuna Akalin Thomas S. Becker Silke Rinkwitz 《Developmental biology》2010,340(2):269-531
Hox genes are key regulators of anterior-posterior axis patterning and have a major role in hindbrain development. The zebrafish Hox4 paralogs have strong overlapping activities in hindbrain rhombomeres 7 and 8, in the spinal cord and in the pharyngeal arches. With the aim to predict enhancers that act on the hoxa4a, hoxb4a, hoxc4a and hoxd4a genes, we used sequence conservation around the Hox4 genes to analyze all fish:human conserved non-coding sequences by reporter assays in stable zebrafish transgenesis. Thirty-four elements were functionally tested in GFP reporter gene constructs and more than 100 F1 lines were analyzed to establish a correlation between sequence conservation and cis-regulatory function, constituting a catalog of Hox4 CNEs. Sixteen tissue-specific enhancers could be identified. Multiple alignments of the CNEs revealed paralogous cis-regulatory sequences, however, the CNE sequence similarities were found not to correlate with tissue specificity. To identify ancestral enhancers that direct Hox4 gene activity, genome sequence alignments of mammals, teleosts, horn shark and the cephalochordate amphioxus, which is the most basal extant chordate possessing a single prototypical Hox cluster, were performed. Three elements were identified and two of them exhibited regulatory activity in transgenic zebrafish, however revealing no specificity. Our data show that the approach to identify cis-regulatory sequences by genome sequence alignments and subsequent testing in zebrafish transgenesis can be used to define enhancers within the Hox clusters and that these have significantly diverged in their function during evolution. 相似文献
62.
Zvonimir Marelja Mita Mullick Chowdhury Carsten Dosche Carsten Hille Otto Baumann Hans-Gerd L?hmannsr?ben Silke Leimkühler 《PloS one》2013,8(4)
In humans, the L-cysteine desulfurase NFS1 plays a crucial role in the mitochondrial iron-sulfur cluster biosynthesis and in the thiomodification of mitochondrial and cytosolic tRNAs. We have previously demonstrated that purified NFS1 is able to transfer sulfur to the C-terminal domain of MOCS3, a cytosolic protein involved in molybdenum cofactor biosynthesis and tRNA thiolation. However, no direct evidence existed so far for the interaction of NFS1 and MOCS3 in the cytosol of human cells. Here, we present direct data to show the interaction of NFS1 and MOCS3 in the cytosol of human cells using Förster resonance energy transfer and a split-EGFP system. The colocalization of NFS1 and MOCS3 in the cytosol was confirmed by immunodetection of fractionated cells and localization studies using confocal fluorescence microscopy. Purified NFS1 was used to reconstitute the lacking molybdoenzyme activity of the Neurospora crassa nit-1 mutant, giving additional evidence that NFS1 is the sulfur donor for Moco biosynthesis in eukaryotes in general. 相似文献
63.
64.
Lineke Begeman Richard Suu-Ire Ashley C. Banyard Christian Drosten Elisa Eggerbauer Conrad M. Freuling Louise Gibson Hooman Goharriz Daniel L. Horton Daisy Jennings Denise A. Marston Yaa Ntiamoa-Baidu Silke Riesle Sbarbaro David Selden Emma L. Wise Thijs Kuiken Anthony R. Fooks Thomas Müller James L. N. Wood Andrew A. Cunningham 《PLoS neglected tropical diseases》2020,14(12)
Rabies is a fatal neurologic disease caused by lyssavirus infection. Bats are important natural reservoir hosts of various lyssaviruses that can be transmitted to people. The epidemiology and pathogenesis of rabies in bats are poorly understood, making it difficult to prevent zoonotic transmission. To further our understanding of lyssavirus pathogenesis in a natural bat host, an experimental model using straw-colored fruit bats (Eidolon helvum) and Lagos bat virus, an endemic lyssavirus in this species, was developed. To determine the lowest viral dose resulting in 100% productive infection, bats in five groups (four bats per group) were inoculated intramuscularly with one of five doses, ranging from 100.1 to 104.1 median tissue culture infectious dose (TCID50). More bats died due to the development of rabies after the middle dose (102.1 TCID50, 4/4 bats) than after lower (101.1, 2/4; 101.1, 2/4) or higher (103.1, 2/4; 104.1, 2/4) doses of virus. In the two highest dose groups, 4/8 bats developed rabies. Of those bats that remained healthy 3/4 bats seroconverted, suggesting that high antigen loads can trigger a strong immune response that abrogates a productive infection. In contrast, in the two lowest dose groups, 3/8 bats developed rabies, 1/8 remained healthy and seroconverted and 4/8 bats remained healthy and did not seroconvert, suggesting these doses are too low to reliably induce infection. The main lesion in all clinically affected bats was meningoencephalitis associated with lyssavirus-positive neurons. Lyssavirus antigen was detected in tongue epithelium (5/11 infected bats) rather than in salivary gland epithelium (0/11), suggesting viral excretion via the tongue. Thus, intramuscular inoculation of 102.1 TCID50 of Lagos bat virus into straw-colored fruit bats is a suitable model for lyssavirus associated bat rabies in a natural reservoir host, and can help with the investigation of lyssavirus infection dynamics in bats. 相似文献
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66.
Ilse Van Gucht Josephina A.N. Meester Jotte Rodrigues Bento Maaike Bastiaansen Jarl Bastianen Ilse Luyckx Lotte Van Den Heuvel Cédric H.G. Neutel Pieter-Jan Guns Mandy Vermont Erik Fransen Melanie H.A.M. Perik Joe Davis Velchev Maaike Alaerts Dorien Schepers Silke Peeters Isabel Pintelon Abdulrahman Almesned Aline Verstraeten 《American journal of human genetics》2021,108(6):1115-1125
67.
Elgar Susanne Quabius Silke Tribius Alessa Heinrichs Dirk Haaser Andr Kühnel Martin Laudien Florian Hoppe Robert Mlynski Petra Ambrosch Markus Hoffmann 《Translational oncology》2021,14(2)
Previous studies describe a correlation between HPV-positivity and non-smoking in TSCC; p16INK4A-expression as surrogate-marker for HPV-DNA/RNA-positivity is discussed controversially. In the present study, these parameters are assessed prospectively. HPV-status of sputum and tonsillar-swabs was analyzed to determine their validity as surrogate-marker for tissue-HPV-status.TSCC- (n = 52) and non-neoplastic tonsillar tissue (n = 163) were analyzed. HPV-DNA- and HPV-RNA-status of total sputum, cellular fraction and supernatants, tonsillar-swabs and -tissue was determined by (RT)-PCR. Immunohistochemistry determined p16INK4A-expression.23/163 (14.2%) non-neoplastic tonsils were HPV-DNA-positive; five patients (3 HPV16, 2 HPV11) had active HPV-infections (HPV-RNA-positive), in all biomaterials. 140/163 (85.9%) patients were either HPV-DNA-positive or HPV-DNA-negative in all samples. 21/52 (40.4%) TSCC-tonsils were HPV-DNA-positive; 17 patients were HPV-RNA-positive (14 HPV16; 4 HPV18). 40/52 (76.9%) TSCC-patients were congruent in all biomaterials. p16INK4A-expression alone would have misclassified the HPV-status of 14/52 (26.2%) TSCC-patients.This prospective study confirms the discrepancy between HPV-status and p16INK4A-expression and the significant correlation between non-smoking and HPV-DNA-positivity. HPV-sputum- and/or swab-results do not consistently match tissue-results, possibly having (detrimental) consequences if those were used to assess tissue-HPV-status. In the 5 patients with active HPV infection in the non-neoplasitic tonsils, tonsillectomy likely prevented subsequent development of TSCC. 相似文献
68.
M. Reimeringer N. Nuño C. Desmarais-Trépanier M. Lavigne P.A. Vendittoli 《Computer methods in biomechanics and biomedical engineering》2013,16(11):1221-1231
One of the crucial factors for short- and long-term clinical success of total hip arthroplasty cementless implants is primary stability. Indeed, motion at the bone–implant interface above 40 μm leads to partial bone ingrowth, while motion exceeding 150 μm completely inhibits bone ingrowth. The aim of this study was to investigate the effect of two cementless femoral stem designs with different lengths on the primary stability. A finite element model of a composite Sawbones® fourth generation, implanted with five lengths of the straight prosthesis design and four lengths of the curved prosthesis design, was loaded with hip joint and abductor forces representing two physiological activities: fast walking and stair climbing. We found that reducing the straight stem length from 146 to 54 mm increased the average micromotion from 17 to 52 μm during fast walking, while the peak value increased from 42 to 104 μm. With the curved stem, reducing length from 105 to 54 mm increased the average micromotion from 10 to 29 μm, while the peak value increased from 37 to 101 μm. Similar findings are obtained for stair climbing for both stems. Although the present study showed that femoral stem length as well as stem design directly influences its primary stability, for the two femoral stems tested, length could be reduced substantially without compromising the primary stability. With the aim of minimising surgical invasiveness, newer femoral stem design and currently well performing stems might be used with a reduced length without compromising primary stability and hence, long-term survivorship. 相似文献
69.
Jessica Fitzgibbon Martina Beck Ji Zhou Christine Faulkner Silke Robatzek Karl Oparka 《The Plant cell》2013,25(1):57-70
Plasmodesmata (PD) form tubular connections that function as intercellular communication channels. They are essential for transporting nutrients and for coordinating development. During cytokinesis, simple PDs are inserted into the developing cell plate, while during wall extension, more complex (branched) forms of PD are laid down. We show that complex PDs are derived from existing simple PDs in a pattern that is accelerated when leaves undergo the sink–source transition. Complex PDs are inserted initially at the three-way junctions between epidermal cells but develop most rapidly in the anisocytic complexes around stomata. For a quantitative analysis of complex PD formation, we established a high-throughput imaging platform and constructed PDQUANT, a custom algorithm that detected cell boundaries and PD numbers in different wall faces. For anticlinal walls, the number of complex PDs increased with increasing cell size, while for periclinal walls, the number of PDs decreased. Complex PD insertion was accelerated by up to threefold in response to salicylic acid treatment and challenges with mannitol. In a single 30-min run, we could derive data for up to 11k PDs from 3k epidermal cells. This facile approach opens the door to a large-scale analysis of the endogenous and exogenous factors that influence PD formation. 相似文献
70.
Chamaida Plasencia Dora Pascual-Salcedo Sara García-Carazo Leticia Lojo Laura Nu?o Alejandro Villalba Diana Peiteado Florencia Arribas Jesus Díez Maria Teresa López-Casla Emilio Martín-Mola Alejandro Balsa 《Arthritis research & therapy》2013,15(4):R79