全文获取类型
收费全文 | 725篇 |
免费 | 66篇 |
出版年
2023年 | 7篇 |
2022年 | 9篇 |
2021年 | 27篇 |
2020年 | 17篇 |
2019年 | 18篇 |
2018年 | 19篇 |
2017年 | 20篇 |
2016年 | 33篇 |
2015年 | 39篇 |
2014年 | 48篇 |
2013年 | 47篇 |
2012年 | 67篇 |
2011年 | 62篇 |
2010年 | 23篇 |
2009年 | 29篇 |
2008年 | 44篇 |
2007年 | 48篇 |
2006年 | 39篇 |
2005年 | 23篇 |
2004年 | 27篇 |
2003年 | 24篇 |
2002年 | 25篇 |
2001年 | 6篇 |
2000年 | 6篇 |
1999年 | 10篇 |
1998年 | 9篇 |
1997年 | 8篇 |
1996年 | 11篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1991年 | 5篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1970年 | 1篇 |
1969年 | 2篇 |
1967年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有791条查询结果,搜索用时 15 毫秒
21.
Livia G. R. P. Macêdo Milena Carvalho-Silva Gabriela K. Ferreira Júlia S. Vieira Natália Olegário Renata C. Gonçalves Francieli S. Vuolo Gustavo C. Ferreira Patrícia F. Schuck Felipe Dal-Pizzol Emilio L. Streck 《Neurochemical research》2013,38(12):2625-2630
Tyrosinemia type II, also known as Richner–Hanhart syndrome, is an autosomal recessive inborn error of metabolism caused by a deficiency of hepatic cytosolic tyrosine aminotransferase, and is associated with neurologic and development difficulties in numerous patients. Considering that the mechanisms underlying the neurological dysfunction in hypertyrosinemic patients are poorly known and that studies demonstrated that high concentrations of tyrosine provoke oxidative stress in vitro and in vivo in the cerebral cortex of rats, in the present study we investigate the oxidative stress parameters (enzymatic antioxidant defenses, thiobarbituric acid-reactive substances and protein carbonyl content) in cerebellum, hippocampus and striatum of 30-old-day rats after acute administration of l-tyrosine. Our results demonstrated that the acute administration of l-tyrosine increased the thiobarbituric acid reactive species levels in hippocampus and the carbonyl levels in cerebellum, hippocampus and striatum. In addition, acute administration of l-tyrosine significantly decreased superoxide dismutase activity in cerebellum, hippocampus and striatum, while catalase was increased in striatum. In conclusion, the oxidative stress may contribute, along with other mechanisms, to the neurological dysfunction characteristic of hypertyrosinemia and the administration of antioxidants may be considered as a potential adjuvant therapy for tyrosinemia, especially type II. 相似文献
22.
M. Zavatti E. Resca L. Bertoni T. Maraldi M. Guida G. Carnevale A. Ferrari A. De Pol 《Life sciences》2013,92(20-21):993-1003
AimsThe phytoestrogen Ferutinin plays an important role in prevention of osteoporosis caused by ovariectomy-induced estrogen deficiency in rats, but there is no evidence of its effect on osteoblastic differentiation in vitro. In this study we investigated the effect of Ferutinin on proliferation and osteoblastic differentiation of two different human stem cells populations, one derived from the amniotic fluid (AFSCs) and the other from the dental pulp (DPSCs).Main methodsAFSCs and DPSCs were cultured in a differentiation medium for 14 or 21 days with or without the addition of Ferutinin at a concentration ranging from 10? 11 to 10? 4 M. 17β-Estradiol was used as a positive drug at 10? 8 M. Cell proliferation and expression of specific osteoblast phenotype markers were analyzed.Key findingsMTT assay revealed that Ferutinin, at concentrations of 10? 8 and 10? 9 M, enhanced proliferation of both AFSCs and DPSCs after 72 h of exposure. Moreover, in both stem cell populations, Ferutinin treatment induced greater expression of the osteoblast phenotype markers osteocalcin (OCN), osteopontin (OPN), collagen I, RUNX-2 and osterix (OSX), increased calcium deposition and osteocalcin secretion in the culture medium compared to controls. These effects were more pronounced after 14 days of culture in both populations.SignificanceThe enhancing capabilities on proliferation and osteoblastic differentiation displayed by the phytoestrogen Ferutinin make this compound an interesting candidate to promote bone formation in vivo. 相似文献
23.
Richard K. Amewu James Chadwick Afthab Hussain Somnath Panda Rinki Rinki Omar Janneh Stephen A. Ward Candel Miguel Hollie Burrell-Saward Livia Vivas Paul M. O’Neill 《Bioorganic & medicinal chemistry》2013,21(23):7392-7397
The synthesis of a range of mono spiro and dispiro 1,2,4,5-tetraoxane dimers is described. Selected molecules were examined in in vitro assays to determine their antimalarial and anticancer potential. Our studies reveal that several molecules possess potent nanomolar antimalarial and single digit micromolar antiproliferative IC50s versus colon (HT29-AK and leukemia (HL60) cell lines. 相似文献
24.
Maria A. De Marco Stefano Porru Paolo Cordioli Bruno M. Cesana Ana Moreno Laura Calzoletti Lebana Bonfanti Arianna Boni Antonio Scotto Di Carlo Cecilia Arici Angela Carta Maria R. Castrucci Isabella Donatelli Paola Tomao Vittoria M. Peri Livia Di Trani Nicoletta Vonesch 《PloS one》2013,8(2)
Background
Pigs play a key epidemiologic role in the ecology of influenza A viruses (IAVs) emerging from animal hosts and transmitted to humans. Between 2008 and 2010, we investigated the health risk of occupational exposure to swine influenza viruses (SIVs) in Italy, during the emergence and spread of the 2009 H1N1 pandemic (H1N1pdm) virus.Methodology/Principal Findings
Serum samples from 123 swine workers (SWs) and 379 control subjects (Cs), not exposed to pig herds, were tested by haemagglutination inhibition (HI) assay against selected SIVs belonging to H1N1 (swH1N1), H1N2 (swH1N2) and H3N2 (swH3N2) subtypes circulating in the study area. Potential cross-reactivity between swine and human IAVs was evaluated by testing sera against recent, pandemic and seasonal, human influenza viruses (H1N1 and H3N2 antigenic subtypes). Samples tested against swH1N1 and H1N1pdm viruses were categorized into sera collected before (n. 84 SWs; n. 234 Cs) and after (n. 39 SWs; n. 145 Cs) the pandemic peak. HI-antibody titers ≥10 were considered positive. In both pre-pandemic and post-pandemic peak subperiods, SWs showed significantly higher swH1N1 seroprevalences when compared with Cs (52.4% vs. 4.7% and 59% vs. 9.7%, respectively). Comparable HI results were obtained against H1N1pdm antigen (58.3% vs. 7.7% and 59% vs. 31.7%, respectively). No differences were found between HI seroreactivity detected in SWs and Cs against swH1N2 (33.3% vs. 40.4%) and swH3N2 (51.2 vs. 55.4%) viruses. These findings indicate the occurrence of swH1N1 transmission from pigs to Italian SWs.Conclusion/Significance
A significant increase of H1N1pdm seroprevalences occurred in the post-pandemic peak subperiod in the Cs (p<0.001) whereas SWs showed no differences between the two subperiods, suggesting a possible occurrence of cross-protective immunity related to previous swH1N1 infections. These data underline the importance of risk assessment and occupational health surveillance activities aimed at early detection and control of SIVs with pandemic potential in humans. 相似文献25.
26.
Anti‐HSV‐1 and HSV‐2 Flavonoids and a New Kaempferol Triglycoside from the Medicinal Plant Kalanchoe daigremontiana
下载免费PDF全文
![点击此处可从《化学与生物多样性》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Fernanda Gouvêa Gomes Ürményi Georgia do Nascimento Saraiva Livia Marques Casanova Amanda dos Santos Matos Luiza Maria de Magalhães Camargo Maria Teresa Villela Romanos Sônia Soares Costa 《化学与生物多样性》2016,13(12):1707-1714
Kalanchoe daigremontiana (Crassulaceae) is a medicinal plant native to Madagascar. The aim of this study was to investigate the flavonoid content of an aqueous leaf extract from K. daigremontiana (Kd), and assess its antiherpetic potential. The major flavonoid, kaempferol 3‐O‐β‐d ‐xylopyranosyl‐(1 → 2)‐α‐l ‐rhamnopyranoside ( 1 ), was isolated from the AcOEt fraction (Kd‐AC). The BuOH‐soluble fraction afforded quercetin 3‐O‐β‐d ‐xylopyranosyl‐(1 → 2)‐α‐l ‐rhamnopyranoside ( 2 ) and the new kaempferol 3‐O‐β‐d ‐xylopyranosyl‐(1 → 2)‐α‐l ‐rhamnopyranoside‐7‐O‐β‐d ‐glucopyranoside ( 3 ), named daigremontrioside. The crude extract, Kd‐AC fraction, flavonoids 1 and 2 were evaluated using acyclovir‐sensitive strains of HSV‐1 and HSV‐2. Kd‐AC was highly active against HSV‐1 (EC50 = 0.97 μg/ml, SI > 206.1) and HSV‐2 (EC50 = 0.72 μg/ml, SI > 277.7). Flavonoids 1 and 2 showed anti‐HSV‐1 (EC50 = 7.4 μg/ml; SI > 27 and EC50 = 5.8 μg/ml; SI > 8.6, respectively) and anti‐HSV‐2 (EC50 = 9.0 μg/ml; SI > 22.2 and EC50 = 36.2 μg/ml; SI > 5.5, respectively) activities, suggesting the contribution of additional substances to the antiviral activity. 相似文献
27.
28.
Juergen Haas Rafal Gumienny Alessandro Barbato Flavio Ackermann Gerardo Tauriello Martino Bertoni Gabriel Studer Anna Smolinski Torsten Schwede 《Proteins》2019,87(12):1378-1387
Critical blind assessment of structure prediction techniques is crucial for the scientific community to establish the state of the art, identify bottlenecks, and guide future developments. In Critical Assessment of Techniques in Structure Prediction (CASP), human experts assess the performance of participating methods in relation to the difficulty of the prediction task in a biennial experiment on approximately 100 targets. Yet, the development of automated computational modeling methods requires more frequent evaluation cycles and larger sets of data. The “Continuous Automated Model EvaluatiOn (CAMEO)” platform complements CASP by conducting fully automated blind prediction evaluations based on the weekly pre-release of sequences of those structures, which are going to be published in the next release of the Protein Data Bank (PDB). Each week, CAMEO publishes benchmarking results for predictions corresponding to a set of about 20 targets collected during a 4-day prediction window. CAMEO benchmarking data are generated consistently for all methods at the same point in time, enabling developers to cross-validate their method's performance, and referring to their results in publications. Many successful participants of CASP have used CAMEO—either by directly benchmarking their methods within the system or by comparing their own performance to CAMEO reference data. CAMEO offers a variety of scores reflecting different aspects of structure modeling, for example, binding site accuracy, homo-oligomer interface quality, or accuracy of local model confidence estimates. By introducing the "bestSingleTemplate" method based on structure superpositions as a reference for the accuracy of 3D modeling predictions, CAMEO facilitates objective comparison of techniques and fosters the development of advanced methods. 相似文献
29.
Effects of UVB radiation on freshwater autotrophic and heterotrophic picoplankton in a subalpine lake 总被引:1,自引:0,他引:1
The effects of UVB radiation on the activity of heterotrophic (HPP) and
autotrophic (APP) picoplankton (0.2-2 m) and
of autotrophic assemblages >2 m has been measured and
compared. Under natural UVB irradiance in a large, deep, oligotrophic
subalpine lake (Lago Maggiore, 4555N) with mean dissolved organic carbon
(DOC) concentrations of 1 mg Cl-1, the
microorganisms of the two size fractions were not significantly
photoinhibited in their autotrophic and heterotrophic activities. The
vertical attenuation coefficient (Kd) for irradiance
at 305 nm ranged from 1.45 to 1.67 during spring and summer. The mixing
layer extended to a greater depth than the layer affected by UVB radiation
(z1% < zmix), thus
enabling the microorganisms living there to photoadapt. As the assimilation
numbers of APP and nanoplankton were higher at 2 m depth than near the
surface, we suspected that the influence of longer wavelength (UVA,
photosynthetically active radiation) could be stronger than UVB in
affecting the photosynthetic efficiency of natural populations. The
artificial increase in UVB irradiance had a higher detrimental effect on
HPP due to their smaller size, less protection and indirect effects through
autotrophic cell inhibition. Picocyanobacteria were percentually more
affected by UVB than nanoplankton during April due to the presence of
diatoms, which are more resistant than other algal groups to solar UVB
irradiance. Furthermore, picocyanobacteria had lower assimilation numbers
with respect to larger phytoplankton in the quartz tubes during
stratification.
相似文献
30.
Jacquamet L Ohana J Joly J Borel F Pirocchi M Charrault P Bertoni A Israel-Gouy P Carpentier P Kozielski F Blot D Ferrer JL 《Structure (London, England : 1993)》2004,12(7):1219-1225
Crystallogenesis, usually based on the vapor diffusion method, is currently considered one of the most difficult steps in macromolecular X-ray crystallography. Due to the increasing number of crystallization assays performed by protein crystallographers, several automated analysis methods are under development. Most of these methods are based on microscope images and shape recognition. We propose an alternative method of identifying protein crystals: by directly exposing the crystallization drops to an X-ray beam. The resulting diffraction provides far more information than classical microscope images. Not only is the presence of diffracting crystals revealed, but also a first estimation of the space group, cell parameters, and mosaicity is obtained. In certain cases, it is also possible to collect enough data to verify the presence of a specific substrate or a heavy atom. All these steps are performed without the sometimes tedious necessity of removing crystals from their crystallization drop. 相似文献