全文获取类型
收费全文 | 3284篇 |
免费 | 193篇 |
出版年
2024年 | 2篇 |
2023年 | 19篇 |
2022年 | 43篇 |
2021年 | 94篇 |
2020年 | 41篇 |
2019年 | 75篇 |
2018年 | 110篇 |
2017年 | 116篇 |
2016年 | 166篇 |
2015年 | 170篇 |
2014年 | 221篇 |
2013年 | 245篇 |
2012年 | 292篇 |
2011年 | 305篇 |
2010年 | 199篇 |
2009年 | 115篇 |
2008年 | 222篇 |
2007年 | 192篇 |
2006年 | 157篇 |
2005年 | 182篇 |
2004年 | 117篇 |
2003年 | 128篇 |
2002年 | 85篇 |
2001年 | 15篇 |
2000年 | 11篇 |
1999年 | 15篇 |
1998年 | 17篇 |
1997年 | 15篇 |
1996年 | 5篇 |
1995年 | 14篇 |
1994年 | 12篇 |
1993年 | 11篇 |
1992年 | 10篇 |
1991年 | 5篇 |
1990年 | 2篇 |
1989年 | 6篇 |
1988年 | 7篇 |
1987年 | 4篇 |
1985年 | 3篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 4篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1967年 | 1篇 |
1957年 | 1篇 |
1955年 | 1篇 |
1954年 | 2篇 |
1948年 | 1篇 |
1945年 | 1篇 |
排序方式: 共有3477条查询结果,搜索用时 15 毫秒
61.
Antonio Díaz-Cruz Raquel Guinzberg Ruy Guerra Magdalena Vilchis Daniel Carrasco Francisco J. García-vázquez 《Free radical research》2013,47(6):663-672
It is known that adrenaline promotes hydroxyl radical generation in isolated rat hepatocytes. The aim of this work was to investigate a potential role of NADPH oxidase (Nox) isoforms for an oxidative stress signal in response to adrenaline in hepatocytes. Enriched plasma membranes from isolated rat liver cells were prepared for this purpose. These membranes showed catalytic activity of Nox isoforms, probably Nox 2 based on its complete inhibition with specific antibodies. NADPH was oxidized to convert O2 into superoxide radical, later transformed into H2O2. This enzymatic activity requires previous activation with either 3 mM Mn2+ or guanosine 5′-0-(3-thiotriphosphate) (GTPγS) plus adrenaline. Experimental conditions for activation and catalytic steps were set up: ATP was not required; S0.5 for NADPH was 44 μM; S0.5 for FAD was 8 μM; NADH up to 1 mM was not substrate, and diphenyleneiodonium was inhibitory. Activation with GTPγS plus adrenaline was dose- and Ca2+-dependent and proceeded through α1-adrenergic receptors (AR), whereas β-AR stimulation resulted in inhibition of Nox activity. These results lead us to propose H2O2 as additional transduction signal for adrenaline response in hepatic cells. 相似文献
62.
Magdalena Świderska Anna Zalewska Joanna Pogorzelska Robert Flisiak Adrian Chabowski 《Free radical research》2013,47(8):841-850
The objective of this study is to determine if treatment with the angiogenesis inhibitor TNP-470 results in impairment of oxidative stress, inhibition of nuclear factor kappa B (NF-κB) activation and decrease of nitric oxide production in an experimental model of rat hepatocarcinogenesis. Tumour was induced by diethylnitrosamine and promoted by two-thirds hepatectomy plus acetaminofluorene administration. Experiments were carried out at 28 weeks after initiating the treatment. TNP-470 was administered at 30 mg/kg, three times per week from 20 to 28 weeks. Carcinomatous tissue growing outside dysplastic nodules and a marked expression of placental glutathione S-transferase were detected in rats with induced carcinogenesis. Liver concentrations of thiobarbituric acid reactive substances, reduced glutathione (GSH) and glutathione disulfide (GSSG) were significantly higher than those of controls and there was a significant increase in the GSSG/GSH ratio. Tumour growth was accompanied by augmented expression of inducible nitric oxide synthase, activation of (NF-κB) and proteolysis of IkappaB. All these effects were absent in animals receiving TNP-470. Our results indicate that TNP-470 inhibits oxidative stress, nitric oxide production and NF-κB activation induced by experimental hepatocarcinogenesis. These changes would contribute to the beneficial effects of TNP-470 in cancer treatment. 相似文献
63.
Vasopressin and oxytocin receptors belong to the superfamily of G protein‐coupled receptors and play an important role in many physiological functions. They are also involved in a number of pathological conditions being important drug targets. In this work, four vasopressin analogues substituted at position 2 with 3,3′‐diphenylalanine have been docked into partially flexible vasopressin and oxytocin receptors. The bulky residue at position 2 acts as a structural restraint much stronger in the oxytocin receptor (OTR) than in the vasopressin V2 receptor (V2R), resulting in a different location of the analogues in these receptors. This explains the different, either agonistic or antagonistic, activities of the analogues in V2R and OTR, respectively. In all complexes, the conserved polar residues serve as anchor points for the ligand both in OTR and V2R. Strong interactions of the C‐terminus of analogue II ([Mpa1,d ‐Dpa2,Val4,d ‐Arg8]VP) with extracellular loop 3 may be responsible for its highest activity at V2R. It also appears that V2R adapts more readily to the docking analogues by conformational changes in the aromatic side chains triggering receptor activation. A weak activity at V1a vasopressin receptor appears to be caused by weak receptor–ligand interactions. Results of this study may facilitate a rational design of new analogues with the highest activity/selectivity at vasopressin and OTRs. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
64.
Joanna Suliburska Pawel Bogdanski Ewa Gajewska Grazyna Kalmus Magdalena Sobieska Wlodzimierz Samborski 《Journal of physiology and biochemistry》2013,69(4):847-853
Some data indicate a potential relationship between insulin resistance level and the concentration of osteoprotegerin (OPG) in the body. There have been few studies concerning OPG level and its relationship with insulin resistance and body composition in young people. The aim of this study was to assess serum osteoprotegerin concentration in obese adolescents, and to evaluate its potential association with insulin resistance. Seventy-eight obese adolescents and 20 healthy volunteers aged 12–18 years were recruited in the study. Selected anthropometrical measurements and blood biochemical analyses were performed. Insulin resistance in the participants was evaluated according to the homeostasis model assessment-insulin resistance (HOMA-IR) protocol. Level of OPG was assessed in serum. Obese subjects had significantly higher HOMA-IR indices and OPG levels in serum than the control group. A significant positive correlation between OPG and insulin resistance was found. It was observed that high concentrations of osteoprotegerin are associated with insulin resistance in obese adolescents. 相似文献
65.
Magdalena Eriksson Bengt Nordeh Bengt Jernström 《Nucleosides, nucleotides & nucleic acids》2013,32(5-6):717-720
Abstract Flow linear dichroism and fluorescence spectroscopy show that the covalent (+)-anti-BPDE-DNA complex adopts two rapidly interchanging conformations. The binding introduces local flexibility in DNA facilitating further covalent attacks. 相似文献
66.
Magdalena Pfister Silke Farkas Ramamurthy Charubala Wolfgang Pfleiderer 《Nucleosides, nucleotides & nucleic acids》2013,32(5-6):595-600
Abstract The usefulness of the p-nitrophenylethylsulfonyl (NPES) group for 2′-OH protection in oligoribonucleotide synthesis is further investigated. The difficulties of uridine protection are discussed and the p-cyanophenylethyl (CPE) group introduced as a versatile new 04-blocking group. 相似文献
67.
Alina Kuzniacka Jolanta Wierzba Magdalena Ratajska Beata S. Lipska Magdalena Koczkowska Monika Malinowska Janusz Limon 《Journal of applied genetics》2013,54(1):27-33
Cornelia de Lange syndrome (CdLS) is a rare multi-system genetic disorder characterised by growth and developmental delay, distinctive facial dysmorphism, limb malformations and multiple organ defects. The disease is caused by mutations in genes responsible for the formation and regulation of cohesin complex. About half of the cases result from mutations in the NIPBL gene coding delangin, a protein regulating the initialisation of cohesion. To date, approximately 250 point mutations have been identified in more than 300 CdLS patients worldwide. In the present study, conducted on a group of 64 unrelated Polish CdLS patients, 25 various NIPBL sequence variants, including 22 novel point mutations, were detected. Additionally, large genomic deletions on chromosome 5p13 encompassing the NIPBL gene locus were detected in two patients with the most severe CdLS phenotype. Taken together, 42 % of patients were found to have a deleterious alteration affecting the NIPBL gene, by and large private ones (89 %). The review of the types of mutations found so far in Polish patients, their frequency and correlation with the severity of the observed phenotype shows that Polish CdLS cases do not significantly differ from other populations. 相似文献
68.
Beata S. Lipska Irena Balasz-Chmielewska Lucyna Morzuch Kacper Wasielewski Dominika Vetter Halina Borzecka Dorota Drozdz Agnieszka Firszt-Adamczyk Ewa Gacka Tomasz Jarmolinski Joanna Ksiazek Elzbieta Kuzma-Mroczkowska Mieczyslaw Litwin Anna Medynska Magdalena Silska Maria Szczepanska Marcin Tkaczyk Anna Wasilewska Franz Schaefer Aleksandra Zurowska Janusz Limon 《Journal of applied genetics》2013,54(3):327-333
Hereditary nephrotic syndrome is caused by mutations in a number of different genes, the most common being NPHS2. The aim of the study was to identify the spectrum of NPHS2 mutations in Polish patients with the disease. A total of 141 children with steroid-resistant nephrotic syndrome (SRNS) were enrolled in the study. Mutational analysis included the entire coding sequence and intron boundaries of the NPHS2 gene. Restriction fragment length polymorphism (RFLP) and TaqMan genotyping assay were applied to detect selected NPHS2 sequence variants in 575 population-matched controls. Twenty patients (14 %) had homozygous or compound heterozygous NPHS2 mutations, the most frequent being c.1032delT found in 11 children and p.R138Q found in four patients. Carriers of the c.1032delT allele were exclusively found in the Pomeranian (Kashubian) region, suggesting a founder effect origin. The 14 % NPHS2 gene mutation detection rate is similar to that observed in other populations. The heterogeneity of mutations detected in the studied group confirms the requirement of genetic testing the entire NPHS2 coding sequence in Polish patients, with the exception of Kashubs, who should be initially screened for the c.1032delT deletion. 相似文献
69.