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941.
Karen Gilio Imke C. A. Munnix Pierre Mangin Judith M. E. M. Cosemans Marion A. H. Feijge Paola E. J. van der Meijden Serv�� Olieslagers Magdalena B. Chrzanowska-Wodnicka Rivka Lillian Simone Schoenwaelder Shigeo Koyasu Stewart O. Sage Shaun P. Jackson Johan W. M. Heemskerk 《The Journal of biological chemistry》2009,284(49):33750-33762
Platelets are activated by adhesion to vascular collagen via the immunoglobulin receptor, glycoprotein VI (GPVI). This causes potent signaling toward activation of phospholipase Cγ2, which bears similarity to the signaling pathway evoked by T- and B-cell receptors. Phosphoinositide 3-kinase (PI3K) plays an important role in collagen-induced platelet activation, because this activity modulates the autocrine effects of secreted ADP. Here, we identified the PI3K isoforms directly downstream of GPVI in human and mouse platelets and determined their role in GPVI-dependent thrombus formation. The targeting of platelet PI3Kα or -β strongly and selectively suppressed GPVI-induced Ca2+ mobilization and inositol 1,4,5-triphosphate production, thus demonstrating enhancement of phospholipase Cγ2 by PI3Kα/β. That PI3Kα and -β have a non-redundant function in GPVI-induced platelet activation and thrombus formation was concluded from measurements of: (i) serine phosphorylation of Akt, (ii) dense granule secretion, (iii) intracellular Ca2+ increases and surface expression of phosphatidylserine under flow, and (iv) thrombus formation, under conditions where PI3Kα/β was blocked or p85α was deficient. In contrast, GPVI-induced platelet activation was insensitive to inhibition or deficiency of PI3Kδ or -γ. Furthermore, PI3Kα/β, but not PI3Kγ, contributed to GPVI-induced Rap1b activation and, surprisingly, also to Rap1b-independent platelet activation via GPVI. Together, these findings demonstrate that both PI3Kα and -β isoforms are required for full GPVI-dependent platelet Ca2+ signaling and thrombus formation, partly independently of Rap1b. This provides a new mechanistic explanation for the anti-thrombotic effect of PI3K inhibition and makes PI3Kα an interesting new target for anti-platelet therapy. 相似文献
942.
Verena Ilona Carrara Julien Zwang Elizabeth A. Ashley Ric N. Price Kasia Stepniewska Marion Barends Alan Brockman Tim Anderson Rose McGready Lucy Phaiphun Stephane Proux Michele van Vugt Robert Hutagalung Khin Maung Lwin Aung Pyae Phyo Piyanuch Preechapornkul Mallika Imwong Sasithon Pukrittayakamee Pratap Singhasivanon Nicholas J. White Fran?ois Nosten 《PloS one》2009,4(2)
Background
Artemisinin combination treatments (ACT) are recommended as first line treatment for falciparum malaria throughout the malaria affected world. We reviewed the efficacy of a 3-day regimen of mefloquine and artesunate regimen (MAS3), over a 13 year period of continuous deployment as first-line treatment in camps for displaced persons and in clinics for migrant population along the Thai-Myanmar border.Methods and Findings
3,264 patients were enrolled in prospective treatment trials between 1995 and 2007 and treated with MAS3. The proportion of patients with parasitaemia persisting on day-2 increased significantly from 4.5% before 2001 to 21.9% since 2002 (p<0.001). Delayed parasite clearance was associated with increased risk of developing gametocytaemia (AOR = 2.29; 95% CI, 2.00–2.69, p = 0.002). Gametocytaemia on admission and carriage also increased over the years (p = 0.001, test for trend, for both). MAS3 efficacy has declined slightly but significantly (Hazards ratio 1.13; 95% CI, 1.07–1.19, p<0.001), although efficacy in 2007 remained well within acceptable limits: 96.5% (95% CI, 91.0–98.7). The in vitro susceptibility of P. falciparum to artesunate increased significantly until 2002, but thereafter declined to levels close to those of 13 years ago (geometric mean in 2007: 4.2 nM/l; 95% CI, 3.2–5.5). The proportion of infections caused by parasites with increased pfmdr1 copy number rose from 30% (12/40) in 1996 to 53% (24/45) in 2006 (p = 0.012, test for trend).Conclusion
Artesunate-mefloquine remains a highly efficacious antimalarial treatment in this area despite 13 years of widespread intense deployment, but there is evidence of a modest increase in resistance. Of particular concern is the slowing of parasitological response to artesunate and the associated increase in gametocyte carriage. 相似文献943.
Reto M. Baertschiger Véronique Serre-Beinier Philippe Morel Domenico Bosco Marion Peyrou Sophie Clément Antonino Sgroi André Kaelin Leo H. Buhler Carmen Gonelle-Gispert 《PloS one》2009,4(8)
Multipotent mesenchymal stromal cells (MSC) are currently investigated clinically as cellular therapy for a variety of diseases. Differentiation of MSC toward endodermal lineages, including hepatocytes and their therapeutic effect on fibrosis has been described but remains controversial. Recent evidence attributed a fibrotic potential to MSC. As differentiation potential might be dependent of donor age, we studied MSC derived from adult and pediatric human bone marrow and their potential to differentiate into hepatocytes or myofibroblasts in vitro and in vivo. Following characterization, expanded adult and pediatric MSC were co-cultured with a human hepatoma cell line, Huh-7, in a hepatogenic differentiation medium containing Hepatocyte growth factor, Fibroblast growth factor 4 and oncostatin M. In vivo, MSC were transplanted into spleen or liver of NOD/SCID mice undergoing partial hepatectomy and retrorsine treatment. Expression of mesenchymal and hepatic markers was analyzed by RT-PCR, Western blot and immunohistochemistry. In vitro, adult and pediatric MSC expressed characteristic surface antigens of MSC. Expansion capacity of pediatric MSC was significantly higher when compared to adult MSC. In co-culture with Huh-7 cells in hepatogenic differentiation medium, albumin expression was more frequently detected in pediatric MSC (5/8 experiments) when compared to adult MSC (2/10 experiments). However, in such condition pediatric MSC expressed alpha smooth muscle more strongly than adult MSC. Stable engraftment in the liver was not achieved after intrasplenic injection of pediatric or adult MSC. After intrahepatic injection, MSC permanently remained in liver tissue, kept a mesenchymal morphology and expressed vimentin and alpha smooth muscle actin, but no hepatic markers. Further, MSC localization merges with collagen deposition in transplanted liver and no difference was observed using adult or pediatric MSC. In conclusion, when transplanted into an injured or regenerating liver, MSC differentiated into myofibroblasts with development of fibrous tissue, regardless of donor age. These results indicate that MSC in certain circumstances might be harmful due to their fibrogenic potential and this should be considered before potential use of MSC for cell therapy. 相似文献
944.
Chalermchai Mitrpant Sue Fletcher Patrick L. Iversen Steve D. Wilton 《The journal of gene medicine》2009,11(1):46-56
Background
Duchenne muscular dystrophy (DMD), a severe neuromuscular disorder, is caused by protein‐truncating mutations in the dystrophin gene. Absence of functional dystrophin renders muscle fibres more vulnerable to damage and necrosis. We report antisense oligomer (AO) induced exon skipping in the B6Ros.Cg‐Dmdmdx–4Cv/J (4CV) mouse, a muscular dystrophy model arising from a nonsense mutation in dystrophin exon 53. Both exons 52 and 53 must be excised to remove the mutation and maintain the reading frame.Methods
A series of 2′‐O‐methyl modified oligomers on a phosphorothioate backbone (2OMeAOs) were designed and evaluated for the removal of each exon, and the most effective compounds were then combined to induce dual exon skipping in both myoblast cultures and in vivo. Exon skipping efficiency of 2OMeAOs and phosphorodiamidate morpholino oligomers (PMOs) was evaluated both in vitro and in vivo at the RNA and protein levels.Results
Compared to the original mdx mouse studies, induction of exon skipping from the 4CV dystrophin mRNA was far more challenging. PMO cocktails could restore synthesis of near‐full length dystrophin protein in cultured 4CV myogenic cells and in vivo, after a single intramuscular injection.Conclusions
By‐passing the protein‐truncating mutation in the 4CV mouse model of muscular dystrophy could not be achieved with single oligomers targeting both exons and was only achieved after the application of AO cocktails to remove exons 52 and 53. As in previous studies, the stability and efficiency of PMOs proved superior to 2OMeAOs for consistent and sustained protein induction in vivo. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献945.
Integrating dark and light bio-hydrogen production strategies: towards the hydrogen economy 总被引:1,自引:0,他引:1
Mark D. Redwood Marion Paterson-Beedle Lynne E. Macaskie 《Reviews in Environmental Science and Biotechnology》2009,8(2):149-185
Biological methods of hydrogen production are preferable to chemical methods because of the possibility to use sunlight, CO2 and organic wastes as substrates for environmentally benign conversions, under moderate conditions. By combining different
microorganisms with different capabilities, the individual strengths of each may be exploited and their weaknesses overcome.
Mechanisms of bio-hydrogen production are described and strategies for their integration are discussed. Dual systems can be
divided broadly into wholly light-driven systems (with microalgae/cyanobacteria as the 1st stage) and partially light-driven
systems (with a dark, fermentative initial reaction). Review and evaluation of published data suggests that the latter type
of system holds greater promise for industrial application. This is because the calculated land area required for a wholly
light-driven dual system would be too large for either centralised (macro-) or decentralised (micro-) energy generation. The
potential contribution to the hydrogen economy of partially light-driven dual systems is overviewed alongside that of other
bio-fuels such as bio-methane and bio-ethanol. 相似文献
946.
Marion Blumenstein Michael T. McMaster Michael A. Black Steven Wu Roneel Prakash Janine Cooney Lesley M. E. McCowan Garth J. S. Cooper Robyn A. North 《Proteomics》2009,9(11):2929-2945
Preeclampsia (PE) is a common, potentially life‐threatening pregnancy syndrome triggered by placental factors released into the maternal circulation, resulting in maternal vascular dysfunction along with activated inflammation and coagulation. Currently there is no screening test for PE. We sought to identify differentially expressed plasma proteins in women who subsequently develop PE that may perform as predictive biomarkers. In seven DIGE experiments, we compared the plasma proteome at 20 wk gestation in women who later developed PE with an appropriate birth weight for gestational age baby (n=27) or a small for gestational age baby (n=12) to healthy controls with uncomplicated pregnancies (n=57). Of the 49 differentially expressed spots associated with PE‐appropriate for gestational age, PE‐small for gestational age or both (p<0.05, false discovery rate corrected), 39 were identified by LC‐MS/MS. Two protein clusters that accurately (>90%) classified women at risk of developing PE were identified. Immunoblots confirmed the overexpression of fibrinogen γ chain and α‐1‐antichymotrypsin in plasma prior to PE. The proteins identified are involved in lipid metabolism, coagulation, complement regulation, extracellular matrix remodeling, protease inhibitor activity and acute‐phase responses, indicating novel synergism between pathways involved in the pathogenesis of PE. Our findings are remarkably similar to recently identified proteins complexed to high‐density lipoprotein and linked to cardiovascular disease. 相似文献
947.
948.
Five constant temperatures between 14 and 30°C were used to evaluate their effect on the development time and adult emergence
of five Trichogramma species found parasitizing eggs of the velvetbean caterpillar Anticarsia gemmatalis Hübner (Lepidoptera: Noctuidae) on soybeans in subtropical Southern Brazil. Host eggs were parasitized at 20°C and then transferred
to the study temperatures to follow development and emergence of parasitoids. All five species were able to develop and emerge
within the range of temperatures evaluated, and the effect of temperature on development rates could be described by linear
regression. Trichogramma acacioi Brun, Moraes & Soares and T. rojasi Nagaraja & Nagarkatti were the most cold-tolerant species, with lower threshold temperatures of 8.1 ± 0.16°C and 9.2 ± 0.16°C,
respectively. Trichogramma atopovirilia Oatman & Platner was the least cold-adapted species, with a lower threshold of 10.2 ± 0.13°C. Degree-day accumulation ranged
from 153.8 DD for T. atopovirilia to 190.7 DD for T. acacioi. Adult emergence was higher than 90% for T. atopovirilia and T. pretiosum at all temperatures, whereas T. lasallei Pinto emergence dropped to 71.3% at 14°C and to 58.3% at 26°C, both significantly lower than the emergence of T. pretiosum and T. atopovirilia. Significantly less T. acacioi adults emerged at 30°C than either T. pretiosum or T. atopovirilia. The sex-ratio was not affected within the range of temperatures studied, and varied from 0.65 to 0.88 (female/(male + female)).
Differences among Trichogramma spp. densities in the field can be attributed to slower development rates and/or reduced emergence of adults, both at low
and high temperatures.
相似文献
Luís A. FoersterEmail: |
949.
950.
Dragan Perovic Jutta Förster Pierre Devaux Djabbar Hariri Morgane Guilleroux Kostya Kanyuka Rebecca Lyons Jens Weyen David Feuerhelm Ute Kastirr Pierre Sourdille Marion Röder Frank Ordon 《Molecular breeding : new strategies in plant improvement》2009,23(4):641-653
Monogenically-inherited resistance to Soil-borne cereal mosaic virus (SBCMV) in hexaploid bread wheat cultivars ‘Tremie’ and ‘Claire’ was mapped on chromosome 5D. The two closest flanking markers
identified in the Claire-derived mapping population, Xgwm469-5D and E37M49, are linked to the resistance locus at distances of 1 and 9 cm, respectively. Xgwm469-5D co-segregated with the SBCMV resistance in the Tremie-derived population and with the recently identified Sbm1 locus in the cv. Cadenza. This suggested that Tremie and Claire carry a resistance gene allelic to Sbm1, or one closely linked to it. The diagnostic value of Xgwm469-5D was assessed using a collection of SBCMV resistant and susceptible cultivars. Importantly, all susceptible genotypes carried
a null allele of Xgwm469-5D, whereas resistant genotypes presumably related to either Claire and Tremie or Cadenza revealed a 152 or 154 bp allele of
Xgwm469-5D, respectively. Therefore, Xgwm469-5D is well suited for marker assisted selection for SBCMV resistance. 相似文献