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131.
132.
Kelitha Maxis Aline Delalandre Johanne Martel-Pelletier Jean-Pierre Pelletier Nicolas Duval Daniel Lajeunesse 《Arthritis research & therapy》2007,8(6):R181
Osteoarthritis (OA) is characterized by articular cartilage degradation and hypertrophic bone changes with osteophyte formation
and abnormal bone remodeling. Two groups of OA patients were identified via the production of variable and opposite levels
of prostaglandin E2 (PGE2) or leukotriene B4 (LTB4) by subchondral osteoblasts, PGE2 levels discriminating between low and high subgroups. We studied whether the expression of 5-lipoxygenase (5-LO) or 5-LO-activating
protein (FLAP) is responsible for the shunt from prostaglandins to leukotrienes. FLAP mRNA levels varied in low and high OA
groups compared with normal, whereas mRNA levels of 5-LO were similar in all osteoblasts. Selective inhibition of cyclooxygenase-2
(COX-2) with NS-398-stimulated FLAP expression in the high OA osteoblasts subgroup, whereas it was without effect in the low
OA osteoblasts subgroup. The addition of PGE2 to the low OA osteoblasts subgroup decreased FLAP expression but failed to affect it in the high OA osteoblasts subgroup.
LTB4 levels in OA osteoblasts were stimulated about twofold by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) plus transforming growth factor-β (TGF-β), a situation corresponding to their effect on FLAP mRNA levels. Treatments with
1,25(OH)2D3 and TGF-β also modulated PGE2 production. TGF-β stimulated PGE2 production in both OA osteoblast groups, whereas 1,25(OH)2D3 alone had a limited effect but decreased the effect of TGF-β in the low OA osteoblasts subgroup. This modulation of PGE2 production was mirrored by the synthesis of COX-2. IL-18 levels were only slightly increased in a subgroup of OA osteoblasts
compared with normal; however, no relationship was observed overall between IL-18 and PGE2 levels in normal and OA osteoblasts. These results suggest that the shunt from the production of PGE2 to LTB4 is through regulation of the expression of FLAP, not 5-LO, in OA osteoblasts. The expression of FLAP in OA osteoblasts is
also modulated differently by 1,25(OH)2D3 and TGF-β depending on their endogenous low and high PGE2 levels. 相似文献
133.
RNA interference (RNAi) is widely used in Caenorhabditis elegans to identify gene function and has been adapted as a high-throughput screening method to identify genes involved in essential processes. The technique has been applied to parasitic nematodes with variable success and we believe that inconsistent outcomes preclude its use as a robust screen with which to identify potential control targets. In this article, key issues that require clarification are discussed, including the mode of delivery of double-stranded RNA to the parasite, the developmental stage targeted and, perhaps of most importance, whether the RNAi pathway (as defined by studies in C. elegans) is fully functional in some parasitic nematodes. 相似文献
134.
Evaluation of blood pressure in feline night monkeys (Aotus azarae infulatus) under different restraint protocols 下载免费PDF全文
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Mineem Saliba Nick Ramalanjaona Sandrine Gulberti Isabelle Bertin-Jung Aline Thomas Samir Dahbi Chrystel Lopin-Bon Jean-Claude Jacquinet Christelle Breton Mohamed Ouzzine Sylvie Fournel-Gigleux 《The Journal of biological chemistry》2015,290(12):7658-7670
Among glycosaminoglycan (GAG) biosynthetic enzymes, the human β1,4-galactosyltransferase 7 (hβ4GalT7) is characterized by its unique capacity to take over xyloside derivatives linked to a hydrophobic aglycone as substrates and/or inhibitors. This glycosyltransferase is thus a prime target for the development of regulators of GAG synthesis in therapeutics. Here, we report the structure-guided design of hβ4GalT7 inhibitors. By combining molecular modeling, in vitro mutagenesis, and kinetic measurements, and in cellulo analysis of GAG anabolism and decorin glycosylation, we mapped the organization of the acceptor binding pocket, in complex with 4-methylumbelliferone-xylopyranoside as prototype substrate. We show that its organization is governed, on one side, by three tyrosine residues, Tyr194, Tyr196, and Tyr199, which create a hydrophobic environment and provide stacking interactions with both xylopyranoside and aglycone rings. On the opposite side, a hydrogen-bond network is established between the charged amino acids Asp228, Asp229, and Arg226, and the hydroxyl groups of xylose. We identified two key structural features, i.e. the strategic position of Tyr194 forming stacking interactions with the aglycone, and the hydrogen bond between the His195 nitrogen backbone and the carbonyl group of the coumarinyl molecule to develop a tight binder of hβ4GalT7. This led to the synthesis of 4-deoxy-4-fluoroxylose linked to 4-methylumbelliferone that inhibited hβ4GalT7 activity in vitro with a Ki 10 times lower than the Km value and efficiently impaired GAG synthesis in a cell assay. This study provides a valuable probe for the investigation of GAG biology and opens avenues toward the development of bioactive compounds to correct GAG synthesis disorders implicated in different types of malignancies. 相似文献
138.
Silencing the expression of the salivary sheath protein causes transgenerational feeding suppression in the aphid Sitobion avenae 总被引:1,自引:0,他引:1 下载免费PDF全文
Aline Koch Jafargholi Imani Andreas Vilcinskas Karl‐Heinz Kogel 《Plant biotechnology journal》2015,13(6):849-857
Aphids produce gel saliva during feeding which forms a sheath around the stylet as it penetrates through the apoplast. The sheath is required for the sustained ingestion of phloem sap from sieve elements and is thought to form when the structural sheath protein (SHP) is cross‐linked by intermolecular disulphide bridges. We investigated the possibility of controlling aphid infestation by host‐induced gene silencing (HIGS) targeting shp expression in the grain aphid Sitobion avenae. When aphids were fed on transgenic barley expressing shp double‐stranded RNA (shp‐dsRNA), they produced significantly lower levels of shp mRNA compared to aphids feeding on wild‐type plants, suggesting that the transfer of inhibitory RNA from the plant to the insect was successful. shp expression remained low when aphids were transferred from transgenic plants and fed for 1 or 2 weeks, respectively, on wild‐type plants, confirming that silencing had a prolonged impact. Reduced shp expression correlated with a decline in growth, reproduction and survival rates. Remarkably, morphological and physiological aberrations such as winged adults and delayed maturation were maintained over seven aphid generations feeding on wild‐type plants. Targeting shp expression therefore appears to cause strong transgenerational effects on feeding, development and survival in S. avenae, suggesting that the HIGS technology has a realistic potential for the control of aphid pests in agriculture. 相似文献
139.
Banchet-Cadeddu A Martinez A Guillarme S Parietti V Monneaux F Hénon E Renault JH Nuzillard JM Haudrechy A 《Bioorganic & medicinal chemistry letters》2011,21(8):2510-2514
Our goal in the search for potentially bioactive analogues of KRN 7000 was to design an easy synthetic approach to a library of analogues using a strategy recently developed in our laboratory based on a Nucleophilic addition followed by an Epoxide Opening (the NEO strategy). Through the use of a common pivotal structure, a new C-galactoside ester analogue (23) was synthesized which showed an encouraging TH2 biased response during preliminary biological tests. 相似文献
140.
Roseane Borner Jo?o Bento-Torres Diego RV Souza Danyelle B Sadala Nonata Trevia José Augusto Farias Nara Lins Aline Passos Amanda Quintairos José Ant?nio Diniz Victor Hugh Perry Pedro Fernando Vasconcelos Colm Cunningham Cristovam W Pican?o-Diniz 《朊病毒》2011,5(3):215-227
Behavioral and neuropathological changes have been widely investigated in murine prion disease but stereological based unbiased estimates of key neuropathological features have not been carried out. After injections of ME7 infected (ME7) or normal brain homogenates (NBH) into dorsal CA1 of albino Swiss mice and C57BL6, we assessed behavioral changes on hippocampal-dependent tasks. We also estimated by optical fractionator at 15 and 18 weeks post-injections (w.p.i.) the total number of neurons, reactive astrocytes, activated microglia and perineuronal nets (PN) in the polymorphic layer of dentate gyrus (PolDG), CA1 and septum in albino Swiss mice. On average, early behavioral changes in albino Swiss mice start four weeks later than in C57BL6. Cluster and discriminant analysis of behavioral data in albino Swiss mice revealed that four of nine subjects start to change their behavior at 12 w.p.i. and reach terminal stage at 22 w.p.i and the remaining subjects start at 22 w.p.i. and reach terminal stage at 26 w.p.i. Biotinylated dextran-amine BDA-tracer experiments in mossy fiber pathway confirmed axonal degeneration and stereological data showed that early astrocytosis, microgliosis and reduction in the perineuronal nets are independent of a change in the number of neuronal cell bodies. Statistical analysis revealed that the septal region had greater levels of neuroinflammation and extracellular matrix damage than CA1. This stereological and multivariate analysis at early stages of disease in an outbred model of prion disease provided new insights connecting behavioral changes and neuroinflammation and seems to be important to understand the mechanisms of prion disease progression.Key words: prion disease, optical fractionator, neuropathology, behavioral changes, albino Swiss mice 相似文献