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排序方式: 共有364条查询结果,搜索用时 31 毫秒
81.
82.
Krueger AC Madigan DL Jiang WW Kati WM Liu D Liu Y Maring CJ Masse S McDaniel KF Middleton T Mo H Molla A Montgomery D Pratt JK Rockway TW Zhang R Kempf DJ 《Bioorganic & medicinal chemistry letters》2006,16(13):3367-3370
Substituted N-alkyl-4-hydroxyquinolon-3-yl-benzothiadiazine sulfamides were investigated as inhibitors of genotype 1 HCV polymerase. Structure-activity relationship patterns for this class of compounds are discussed. 相似文献
83.
Anna Sparatore Elena Perrino Valerio Tazzari Daniela Giustarini Ranieri Rossi Giuseppe Rossoni Kati Erdman Henning Schröder Piero Del Soldato 《Free radical biology & medicine》2009,46(5):586-592
The pharmacological profile of a new, safe, and effective hydrogen sulfide (H2S)-releasing derivative of aspirin (ACS14) is described. We report the synthesis of ACS14, and of its deacetylated metabolite (ACS21), the preliminary pharmacokinetics, and its in vivo metabolism, with the H2S plasma levels after intravenous administration in the rat. ACS14 maintains the thromboxane-suppressing activity of the parent compound, but seems to spare the gastric mucosa, by affecting redox imbalance through increased H2S/glutathione formation, heme oxygenase-1 promoter activity, and isoprostane suppression. 相似文献
84.
Maria H. Alanne Kati Pummi Anthony M. Heape Reidar Gr��nman Juha Peltonen Sirkku Peltonen 《The journal of histochemistry and cytochemistry》2009,57(6):523-529
Tight junctions (TJs) form physical barriers in various tissues and regulate paracellular transport of ions, water, and molecules. Myelinating Schwann cells form highly organized structures, including compact myelin, nodes of Ranvier, paranodal regions, Schmidt-Lanterman incisures, periaxonal cytoplasmic collars, and mesaxons. Autotypic TJs are formed in non-compacted myelin compartments between adjacent membrane lamellae of the same Schwann cell. Using indirect immunofluorescence and RT-PCR, we analyzed the expression of adherens junction (E-cadherin) and TJ [claudins, zonula occludens (ZO)-1, occludin] components in human peripheral nerve endoneurium, showing clear differences with published rodent profiles. Adult nerve paranodal regions contained E-cadherin, claudin-1, claudin-2, and ZO-1. Schmidt-Lanterman incisures contained E-cadherin, claudin-1, claudin-2, claudin-3, claudin-5, ZO-1, and occludin. Mesaxons contained E-cadherin, claudin-1, claudin-2, claudin-3, ZO-1, and occludin. None of the proteins studied were associated with nodal inter-Schwann cell junctions. Fetal nerve expression of claudin-1, claudin-3, ZO-1, and occludin was predominantly punctate, with a mesaxonal labeling pattern, but paranodal (ZO-1, claudin-3) and Schmidt-Lanterman incisure (claudins-1 and -3) expression profiles typical of compact myelin were visible by gestational week 37. The clear differences observed between human and published rodent nerve profiles emphasize the importance of human studies when translating the results of animal models to human diseases. (J Histochem Cytochem 57:523–529, 2009) 相似文献
85.
Lotta Koskinen Jihane Romanos Katri Kaukinen Kirsi Mustalahti Ilma Korponay-Szabo Donatella Barisani Maria Teresa Bardella Fabiana Ziberna Serena Vatta György Széles Zsuzsa Pocsai Kati Karell Katri Haimila Róza Ádány Tarcisio Not Alessandro Ventura Markku Mäki Jukka Partanen Cisca Wijmenga Päivi Saavalainen 《Immunogenetics》2009,61(4):247-256
Human leukocyte antigen (HLA) genes, located on chromosome 6p21.3, have a crucial role in susceptibility to various autoimmune
and inflammatory diseases, such as celiac disease and type 1 diabetes. Certain HLA heterodimers, namely DQ2 (encoded by the
DQA1*05 and DQB1*02 alleles) and DQ8 (DQA1*03 and DQB1*0302), are necessary for the development of celiac disease. Traditional
genotyping of HLA genes is laborious, time-consuming, and expensive. A novel HLA-genotyping method, using six HLA-tagging
single-nucleotide polymorphisms (SNPs) and suitable for high-throughput approaches, was described recently. Our aim was to
validate this method in the Finnish, Hungarian, and Italian populations. The six previously reported HLA-tagging SNPs were
genotyped in patients with celiac disease and in healthy individuals from Finland, Hungary, and two distinct regions of Italy.
The potential of this method was evaluated in analyzing how well the tag SNP results correlate with the HLA genotypes previously
determined using traditional HLA-typing methods. Using the tagging SNP method, it is possible to determine the celiac disease
risk haplotypes accurately in Finnish, Hungarian, and Italian populations, with specificity and sensitivity ranging from 95%
to 100%. In addition, it predicts homozygosity and heterozygosity for a risk haplotype, allowing studies on genotypic risk
effects. The method is transferable between populations and therefore suited for large-scale research studies and screening
of celiac disease among high-risk individuals or at the population level.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Lotta Koskinen and Jihane Romanos are authors with equal contribution. 相似文献
86.
Background
Tumor-stroma reaction is associated with activation of fibroblasts. Nemosis is a novel type of fibroblast activation. It leads to an increased production of growth factors and proinflammatory and proteolytic proteins, while at the same time cytoskeletal proteins are degraded. Here we used paired normal skin fibroblasts and cancer-associated fibroblasts (CAF) and primary and recurrent oral squamous cell carcinoma (SCC) cells to study the nemosis response.Principal Findings
Fibroblast nemosis was analyzed by protein and gene expression and the paracrine regulation with colony formation assay. One of the normal fibroblast strains, FB-43, upregulated COX-2 in nemosis, but FB-74 cells did not. In contrast, CAF-74 spheroids expressed COX-2 but CAF-43 cells did not. Alpha-SMA protein was expressed in both CAF strains and in FB-74 cells, but not in FB-43 fibroblasts. Its mRNA levels were downregulated in nemosis, but the CAFs started to regain the expression. FSP1 mRNA was downregulated in normal fibroblasts and CAF-74 cells, but not in CAF-43 fibroblasts. Serine protease FAP was upregulated in all fibroblasts, more so in nemotic CAFs. VEGF, HGF/SF and FGF7 mRNA levels were upregulated to variable degree in nemosis. CAFs increased the colony formation of primary tumor cell lines UT-SCC-43A and UT-SCC-74A, but normal fibroblasts inhibited the anchorage-independent growth of recurrent UT-SCC-43B and UT-SCC-74B cells.Conclusions
Nemosis response, as observed by COX-2 and growth factor induction, and expression of CAF markers α-SMA, FSP1 and FAP, varies between fibroblast populations. The expression of CAF markers differs between normal fibroblasts and CAFs in nemosis. These results emphasize the heterogeneity of fibroblasts and the evolving tumor-promoting properties of CAFs. 相似文献87.
88.
89.
Patrick Constantinescu Kati Kovacevic Giel J.C.G.M. Bosman Ronald Sluyter 《生物化学与生物物理学报:生物膜》2010,1798(9):1797-1804
Extracellular ATP induces cation fluxes in and impairs the growth of murine erythroleukemia (MEL) cells in a manner characteristic of the purinergic P2X7 receptor, however the presence of P2X7 in these cells is unknown. This study investigated whether MEL cells express functional P2X7. RT-PCR, immunoblotting and immunofluorescence staining demonstrated the presence of P2X7 in MEL cells. Cytofluorometric measurements demonstrated that ATP induced ethidium+ uptake into MEL cells in a concentration-dependent fashion and with an EC50 of ∼ 154 μM. The most potent P2X7 agonist 2′- and 3′-0(4-benzoylbenzoyl) ATP, but not ADP or UTP, induced ethidium+ uptake. ATP-induced ethidium+ and YO-PRO-12+ uptake were impaired by the P2X7 antagonist, A-438079. A colourmetric assay demonstrated that ATP impaired MEL cell growth. A cytofluorometric assay showed that ATP induced MEL cell death and that this process was impaired by A-438079. Finally, cytofluorometric measurements of Annexin-V binding and bio-maleimide staining demonstrated that ATP could induce rapid phosphatidylserine exposure and microparticle release in MEL cells respectively, both of which were impaired by A-438079. These results demonstrate that MEL cells express functional P2X7, and indicate that activation of this receptor may be important in the death and release of microparticles from red blood cells in vivo. 相似文献
90.
Vesna Ilić Aleksandra Krstić Sofija Katić-Radivojević Gordana Jovčić Pavle Milenković Diana Bugarski 《Parasitology international》2010,59(1):82-88
Syphacia obvelata is a rodent nematode parasite with high prevalence in laboratory mice. In our previous work we have demonstrated that this gut-dwelling helminth induces significant hematopoietic changes, characterized by increased myelopoiesis and erythropoiesis in infected animals, and accompanied with altered reactivity of bone marrow hematopoietic progenitors to interleukin (IL)-17. In this study we extended these investigations by demonstrating that naturally acquired S. obvelata infection induces significant alterations in murine bone marrow cells manifested at the molecular level. Namely, S. obvelata infection induced sustained phosphorylation of the members of three major groups of distinctly regulated mitogen-activated protein kinases (MAPKs), the p38, the c-Jun amino-terminal kinase (JNK) and the extracellular signal-regulated kinase (ERK), as well as enhanced expression of mRNA for the inducible nitric oxide synthase (iNOS) in the bone marrow cells of infected animals. Furthermore, the infection interfered with the IL-17-mediated effects in bone marrow cells, since in normal mice IL-17 significantly enhanced phosphorylation of p38 MAPK and upregulated the expression of iNOS and the constitutive, endothelial (e)NOS mRNA, while in S. obvelata-infected animals IL-17 did not influence the MAPKs activation, but markedly down-regulated the expression of both NOS isoforms. The data obtained demonstrating that S. obvelata is able to manipulate signal transduction pathways in the hosts' bone marrow cells, pointed to the multiple layers of immunomodulatory ability of this pinworm parasite and highlighted the importance of working under pinworm-free conditions when using experimental murine models for immunohematopoietic investigations. 相似文献