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941.
Lilian Quero Marina Klawitter Anja Schmaus Melanie Rothley Jonathan Sleeman André N Tiaden Juergen Klasen Norbert Boos Michael O Hottiger Karin Wuertz Peter J Richards 《Arthritis research & therapy》2013,15(4):R94
Introduction
Intervertebral disc (IVD) degeneration is characterized by extracellular matrix breakdown and is considered to be a primary cause of discogenic back pain. Although increases in pro-inflammatory cytokine levels within degenerating discs are associated with discogenic back pain, the mechanisms leading to their overproduction have not yet been elucidated. As fragmentation of matrix components occurs during IVD degeneration, we assessed the potential involvement of hyaluronic acid fragments (fHAs) in the induction of inflammatory and catabolic mediators.Methods
Human IVD cells isolated from patient biopsies were stimulated with fHAs (6 to 12 disaccharides) and their effect on cytokine and matrix degrading enzyme production was assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). The involvement of specific cell surface receptors and signal transduction pathways in mediating the effects of fHAs was tested using small interfering RNA (siRNA) approaches and kinase inhibition assays.Results
Treatment of IVD cells with fHAs significantly increased mRNA expression levels of interleukin (IL)-1β, IL-6, IL-8, cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-1 and -13. The stimulatory effects of fHAs on IL-6 protein production were significantly impaired when added to IVD cells in combination with either Toll-like receptor (TLR)-2 siRNA or a TLR2 neutralizing antibody. Furthermore, the ability of fHAs to enhance IL-6 and MMP-3 protein production was found to be dependent on the mitogen-activated protein (MAP) kinase signaling pathway.Conclusions
These findings suggest that fHAs may have the potential to mediate IVD degeneration and discogenic back pain through activation of the TLR2 signaling pathway in resident IVD cells. 相似文献942.
943.
Felix R. Stahl Katrin Heller Stephan Halle Kirsten A. Keyser Andreas Busche Anja Marquardt Karen Wagner Jasmin Boelter Yvonne Bischoff Elisabeth Kremmer Ramon Arens Martin Messerle Reinhold F?rster 《PLoS pathogens》2013,9(12)
Neonates, including mice and humans, are highly susceptible to cytomegalovirus (CMV) infection. However, many aspects of neonatal CMV infections such as viral cell tropism, spatio-temporal distribution of the pathogen as well as genesis of antiviral immunity are unknown. With the use of reporter mutants of the murine cytomegalovirus (MCMV) we identified the lung as a primary target of mucosal infection in neonatal mice. Comparative analysis of neonatal and adult mice revealed a delayed control of virus replication in the neonatal lung mucosa explaining the pronounced systemic infection and disease in neonates. This phenomenon was supplemented by a delayed expansion of CD8+ T cell clones recognizing the viral protein M45 in neonates. We detected viral infection at the single-cell level and observed myeloid cells forming “nodular inflammatory foci” (NIF) in the neonatal lung. Co-localization of infected cells within NIFs was associated with their disruption and clearance of the infection. By 2-photon microscopy, we characterized how neonatal antigen-presenting cells (APC) interacted with T cells and induced mature adaptive immune responses within such NIFs. We thus define NIFs of the neonatal lung as niches for prolonged MCMV replication and T cell priming but also as sites of infection control. 相似文献
944.
945.
Matthias Dolek Anja Freese-Hager Adi Geyer Emilio Balletto Simona Bonelli 《Journal of Insect Conservation》2013,17(2):357-366
Globally, Euphydryas maturna is a polyphagous butterfly species. At our study sites in Italy and Germany however, the plant used for egg-laying was almost exclusively Fraxinus excelsior. Nevertheless, in Germany, two egg-batches were found on Ligustrum vulgare and one on Viburnum opulus. Females lay their egg-batches at low heights and mostly on small trees (but not <1 m). At the end of the flight season, small egg-batches are laid and we conclude that these are late batches laid by “old females”. Egg-batches and pre-diapause larval webs are often clustered on certain trees and even leaves. This was shown to be a result of female behaviour and not of habitat quality, since the trees chosen were different in subsequent years. Individual females may return for laying further egg-batches to the place of the first egg-deposition and other females follow, since the survival of pre-diapause larvae is higher when more larval webs are on one tree. A further possible advantage during hibernation is discussed. In Italy, post-hibernation larvae form two distinct cohorts: larvae feeding on herbaceous plants (Plantago major, P. minor, Veronica hederifolia), and larvae feeding on Fraxinus excelsior. Although the latter group starts feeding later and pupates later, it reaches the same pupation weight. At our German site, post-hibernation larvae were found almost exclusively on F. excelsior. In fact, we observed larvae searching for food on F. excelsior while the buds of this tree were still closed. We also found larvae searching for food in the herbal layer without finding suitable plants. In some areas, larvae have to wait for the buds of the ash tree to open. Our data suggest that conservation strategies for E. maturna must be site specific according to food plant use of pre- and post-hibernation larvae and habitat type. 相似文献
946.
947.
Emanuele Ricci Graziella Vanosi Andrea Lindenmair Simone Hennerbichler Anja Peterbauer-Scherb Susanne Wolbank Anna Cargnoni Patrizia Bonassi Signoroni Marino Campagnol Christian Gabriel Heinz Redl Ornella Parolini 《Cell and tissue banking》2013,14(3):475-488
The human amniotic membrane (hAM), thanks to its favorable properties, including anti-inflammatory, anti-fibrotic and pro-regenerative effects, is a well-known surgical material for many clinical applications, when used both freshly after isolation and after preservation. We have shown previously that hAM patching is a potential approach to counteract liver fibrosis. Indeed, when fresh hAM was used to cover the liver surface of rats with liver fibrosis induced by the bile duct ligation (BDL) procedure, the progression and severity of fibrosis were significantly reduced. Since cryopreservation enables safety and long-term storage of hAM but may influence its functional properties, here we compared the anti-fibrotic effects of fresh and cryopreserved hAM in rats with BDL-induced liver fibrosis. After BDL, the rat liver was covered with a piece of fresh or cryopreserved hAM, or left untreated. Six weeks later, the degree of liver fibrosis was assessed histologically using the Knodell and the METAVIR scoring systems. Digital image analysis was used to quantify the percentage of the areas of each liver section displaying ductular reaction, extracellular matrix (ECM) deposition, activated myofibroblasts and hepatic stellate cells (HSCs). Liver collagen content was also determined by spectrophotometric technique. The degree of liver fibrosis, ductular reaction, ECM deposition, and the number of activated myofibroblasts and HSCs were all significantly reduced in hAM-treated rats compared to control animals. Fresh and cryopreserved hAM produced the same anti-fibrotic effects. These findings indicate that cryopreservation maintains the anti-fibrotic properties of hAM when used as a patch to reduce the severity of liver fibrosis. 相似文献
948.
949.
We investigated whether acute iron intoxication causes oxidative DNA damage, measured in terms of 7-hydro-8-oxo-2′-deoxyguanosine, 8-oxodG, in nuclear DNA in testes and epididymal sperm cells in vivo and in vitro in rats. In addition, we investigated levels of the modified nucleoside in liver and kidney and measured its urinary excretion.Sperm cells were isolated from the epididymides and the testes cells were isolated after homogenisation. In vitro, the sperm and testes cells were incubated with increasing concentrations of FeCl2 ranging from 0 to 600 μM. The median (range) levels of 8-oxodG/105 dG in the epididymal sperm cells increased from 0.48 (0.42–0.90) to 15.1 (11.4–17.6) (p < 0.05), whereas the level rose from 0.63 (0.22–0.81) to 8.8 (4.5–11.6) (p < 0.05) at 0 and 600 μM, respectively, in the testicular cells.In vivo groups of 7–8 rats received 0, 200 or 400 mg iron/kg as dextran i.p. After 24h, epididymal sperm cells, testes, kidneys and liver were collected for analysis. Kidney and sperm DNA showed a significant increase in 8-oxodG in the iron-treated animals. The median (range) values of the 8-oxodG/105 dG in the epididymal sperm cells rose from 0.66 (0.38–1.09) to 1.12 (0.84–5.88) (p < 0.05) at 0 and 400 mg iron/kg, respectively, whereas the values in the testes and liver showed no significant change. In the kidneys the 8-oxodG/105 dG median (range) values were 0.98 (0.73–1.24), 1.21 (1.13–1.69) and 1.34 (1.12–1.66) after 0, 200 and 400 mg iron/kg, respectively (p < 0.05).The 8-oxodG-excretion rate was measured in 24 h urine before and after iron treatment. The rate of urinary 8-oxodG excretion increased from 129 (104–179) pmol/24 h before treatment to 147 (110–239) pmol/24h after treatment in the group receiving 400 mg iron/kg (p < 0.05).The results indicate that acute iron intoxication may increase oxidative damage to sperm and kidney DNA. 相似文献
950.