全文获取类型
收费全文 | 191篇 |
免费 | 5篇 |
国内免费 | 1篇 |
专业分类
197篇 |
出版年
2022年 | 3篇 |
2021年 | 6篇 |
2020年 | 2篇 |
2019年 | 3篇 |
2018年 | 4篇 |
2017年 | 2篇 |
2016年 | 2篇 |
2015年 | 9篇 |
2014年 | 13篇 |
2013年 | 9篇 |
2012年 | 24篇 |
2011年 | 10篇 |
2010年 | 8篇 |
2009年 | 7篇 |
2008年 | 7篇 |
2007年 | 6篇 |
2006年 | 5篇 |
2005年 | 4篇 |
2004年 | 11篇 |
2003年 | 3篇 |
2002年 | 3篇 |
2001年 | 2篇 |
2000年 | 3篇 |
1999年 | 4篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1994年 | 2篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1964年 | 1篇 |
1957年 | 1篇 |
1949年 | 1篇 |
1945年 | 1篇 |
1939年 | 2篇 |
1938年 | 3篇 |
1937年 | 4篇 |
排序方式: 共有197条查询结果,搜索用时 0 毫秒
61.
The discovery of a selective, high affinity A(2B) adenosine receptor antagonist for the potential treatment of asthma 总被引:2,自引:0,他引:2
Zablocki J Kalla R Perry T Palle V Varkhedkar V Xiao D Piscopio A Maa T Gimbel A Hao J Chu N Leung K Zeng D 《Bioorganic & medicinal chemistry letters》2005,15(3):609-612
Adenosine has been suggested to play a role in asthma, possibly via activation of A(2B) adenosine receptors on mast cells and other pulmonary cells. We describe our initial efforts to discover a xanthine based selective A(2B) AdoR antagonist that resulted in the discovery of CVT-5440, a high affinity A(2B) AdoR antagonist with good selectivity (A(2B) AdoR K(i)=50 nM, selectivity A(1)>200: A(2A)>200: A(3)>167). 相似文献
62.
Ubydul Haque Masahiro Hashizume Gregory E. Glass Ashraf M. Dewan Hans J. Overgaard Taro Yamamoto 《PloS one》2010,5(12)
Background
Malaria is a major public health problem in Bangladesh, frequently occurring as epidemics since the 1990s. Many factors affect increases in malaria cases, including changes in land use, drug resistance, malaria control programs, socioeconomic issues, and climatic factors. No study has examined the relationship between malaria epidemics and climatic factors in Bangladesh. Here, we investigate the relationship between climatic parameters [rainfall, temperature, humidity, sea surface temperature (SST), El Niño-Southern Oscillation (ENSO), the normalized difference vegetation index (NDVI)], and malaria cases over the last 20 years in the malaria endemic district of Chittagong Hill Tracts (CHT).Methods and Principal Findings
Monthly malaria case data from January 1989 to December 2008, monthly rainfall, temperature, humidity sea surface temperature in the Bay of Bengal and ENSO index at the Niño Region 3 (NIÑO3) were used. A generalized linear negative binomial regression model was developed using the number of monthly malaria cases and each of the climatic parameters. After adjusting for potential mutual confounding between climatic factors there was no evidence for any association between the number of malaria cases and temperature, rainfall and humidity. Only a low NDVI was associated with an increase in the number of malaria cases. There was no evidence of an association between malaria cases and SST in the Bay of Bengal and NIÑO3.Conclusion and Significance
It seems counterintuitive that a low NDVI, an indicator of low vegetation greenness, is associated with increases in malaria cases, since the primary vectors in Bangladesh, such as An. dirus, are associated with forests. This relationship can be explained by the drying up of rivers and streams creating suitable breeding sites for the vector fauna. Bangladesh has very high vector species diversity and vectors suited to these habitats may be responsible for the observed results. 相似文献63.
64.
Steven N. Quayle Jennifer Y. Lee Lydia W T. Cheung Li Ding Ruprecht Wiedemeyer Robert W. Dewan Emmet Huang-Hobbs Li Zhuang Richard K. Wilson Keith L. Ligon Gordon B. Mills Lewis C. Cantley Lynda Chin 《PloS one》2012,7(11)
The phosphoinositide 3-kinase (PI3K) pathway is targeted for frequent alteration in glioblastoma (GBM) and is one of the core GBM pathways defined by The Cancer Genome Atlas. Somatic mutations of PIK3R1 are observed in multiple tumor types, but the tumorigenic activity of these mutations has not been demonstrated in GBM. We show here that somatic mutations in the iSH2 domain of PIK3R1 act as oncogenic driver events. Specifically, introduction of a subset of the mutations identified in human GBM, in the nSH2 and iSH2 domains, increases signaling through the PI3K pathway and promotes tumorigenesis of primary normal human astrocytes in an orthotopic xenograft model. Furthermore, we show that cells that are dependent on mutant P85α-mediated PI3K signaling exhibit increased sensitivity to a small molecule inhibitor of AKT. Together, these results suggest that GBM patients whose tumors carry mutant PIK3R1 alleles may benefit from treatment with inhibitors of AKT. 相似文献
65.
66.
Adults of the human parasitic trematode Schistosoma mansoni, which causes
hepatosplenic/intestinal complications in humans, synthesize
glycoconjugates containing the Lewis x (Lex) Galbeta1-->4(Fucalpha1--
>3)GlcNAcbeta1-->R, but not sialyl Lewis x (sLex), antigen. We now
report on our analyses of Lexand sLexexpression in S.haematobium and
S.japonicum, which are two other major species of human schistosomes that
cause disease, and the possible autoimmunity to these antigens in infected
individuals. Antigen expression was evaluated by both ELISA and Western
blot analyses of detergent extracts of parasites using monoclonal
antibodies. Several high molecular weight glycoproteins in both S.
haematobium and S. japonicum contain the Lexantigen, but no sialyl
Lexantigen was detected. In addition, sera from humans and rodents infected
with S.haematobium and S.japonicum contain antibodies reactive with Lex.
These results led us to investigate whether Lexantigens are expressed in
other helminths, including the parasitic trematode Fasciola hepatica , the
parasitic nematode Dirofilaria immitis (dog heartworm), the ruminant
nematode Haemonchus contortus , and the free-living nematode Caenorhabditis
elegans . Neither Lexnor sialyl-Lexis detectable in these other helminths.
Furthermore, none of the helminths, including schistosomes, express Lea,
Leb, Ley, or the H- type 1 antigen. However, several glycoproteins from all
helminths analyzed are bound by Lotus tetragonolobus agglutinin , which
binds Fucalpha1-->3GlcNAc, and Wisteria floribunda agglutinin, which
binds GalNAcbeta1-->4GlcNAc (lacdiNAc or LDN). Thus, schistosomes may be
unique among helminths in expressing the Lexantigen, whereas many different
helminths may express alpha1,3-fucosylated glycans and the LDN motif.
相似文献
67.
BACKGROUND:
Paraoxonase (PON1) can hydrolyze organophosphate pesticides (OP) and has a key role in the susceptibility of human in OP toxicity. The human-enzyme shows polymorphism and variations in the distribution profile of its phenotypes among different ethnic groups have been observed.AIMS:
To see the distribution pattern of total PON1 activity in 45 healthy attendants of poisoning cases; 121 healthy unrelated farm-labours and 59 normal subjects of trauma.MATERIALS AND METHODS:
The PON1 activities from serum/plasma samples of these healthy normal individuals were estimated with/without addition of 1M NaCl in order to determine salt-stimulated and basal activity. The PON 1 phenotypes were determined on the basis of percent activation of enzyme activity.RESULTS:
Tri-modal distribution of basal PON1 activity was observed among all these individuals. 52.0% of the individuals belonged to Phenotype A, 46.6% to phenotype AB while 1.4% to Phenotype B with gene frequency of allele-A and allele-B being 0.753 and 0.247 respectively in excellent agreement with Hardy-Weinberg equilibrium.CONCLUSION:
Maximum number of individuals belonged to phenotype-A (low PON1 activity) showing potential vulnerability towards Op-poisoning. 相似文献68.
A high yield of nifedipine-chitosan microspheres could be obtained using an emulsification phase-separation method. A high level of entrapment of nifedipine in the microspheres was achieved. The microspheres exhibited excellent swelling properties. Differential scanning calorimetry, X-ray diffractometry, and scanning electron microscopy confirmed that at 1.84% loading, nifedipine was dispersed molecularly. The microspheres exhibited faster release at low loadings compared to high loadings. Fitting the data to the coupled Fickian/case II equation, showed that at low loadings polymer relaxation coefficients (k2) were high. As the polymer content increased in the microspheres, the value of n (diffusional exponent characteristic of the release mechanism) approached one, which is indicative of zero order. 相似文献
69.
Shankargouda Patil Hytham N. Fageeh Hammam Ibrahim Fageeh Wael Ibraheem Abdulrahman Saleh Alshehri Ashraf Al-Brakati Salem Almoammar Mohammad Almagbol Harisha Dewan Samar Saeed Khan Hosam Ali Baeshen Vikrant R Patil A. Thirumal Raj Shilpa Bhandi 《Saudi Journal of Biological Sciences》2022,29(5):3568-3576
Gingival mesenchymal stem cells (GMSCs) have significant regenerative potential. Their potential applications range from the treatment of inflammatory diseases, wound healing, and oral disorders. Preconditioning these stem cells can optimize their biological properties. Hypoxia preconditioning of MSCs improves stem cell properties like proliferation, survival, and differentiation potential. This research explored the possible impact of hypoxia on the pluripotent stem cell properties that GMSCs possess. We evaluated the morphology, stemness, neurotrophic factors, and stemness-related genes. We compared the protein levels of secreted neurotrophic factors between normoxic and hypoxic GMSC-conditioned media (GMSC-CM). Results revealed that hypoxic cultured GMSC’s had augmented expression of neurotrophic factors BDNF, GDNF, VEGF, and IGF1 and stemness-related gene NANOG. Hypoxic GMSCs showed decreased expression of the OCT4 gene. In hypoxic GMSC-CM, the neurotrophic factors secretions were significantly higher than normoxic GMSC-CM. Our data demonstrate that culturing of GMSCs in hypoxia enhances the secretion of neurotrophic factors that can lead to neuronal lineage differentiation. 相似文献
70.
Pothukuchi M Nagaraja SB Kelamane S Satyanarayana S Shashidhar Babu S Dewan P Wares F 《PloS one》2011,6(7):e22500