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121.
Hao J Chen B Yao Y Hossain M Nagatomo T Yao H Kong L Sun H 《Bioorganic & medicinal chemistry letters》2012,22(10):3441-3444
Naftidrofuryl oxalate (Praxilene®, 1) has been used for the treatment of intermittent claudication for more than 30 years. It selectively blocks vascular and platelet 5-hydroxytryptamine 2 (5-HT2) receptors. This drug is marketed as a mixture of four stereoisomers, and so far there is no individual biological evaluation on the single isomers. The purpose of this study is to provide an improved method for the preparation of all four stereoisomers of naftidrofuryl, and more importantly, to distinguish them in terms of their binding affinity to 5-hydroxytryptamine 2A (5-HT2A) receptor. The bioassay results revealed that the C-2S configuration of naftidrofuryl was crucial for the binding affinity with 5-HT2A receptor, and the C-2′ configuration was less important for binding. In conclusion, our study may pave the way to develop single naftidrofuryl isomers with C-2S configuration as inhibitors of 5-HT2A receptor that have clinical significance as vasodilators and CNS agents. 相似文献
122.
DIMINUTO 1 affects the lignin profile and secondary cell wall formation in Arabidopsis 总被引:1,自引:0,他引:1
Brassinosteroids (BRs) play a crucial role in plant growth and development and DIMINUTO 1 (DIM1), a protein involved in BR
biosynthesis, was previously identified as a cell elongation factor in Arabidopsis thaliana. Through promoter expression analysis, we showed that DIM1 was expressed in most of the tissue types in seedlings and sectioning of the inflorescence stem revealed that DIM1 predominantly
localizes to the xylem vessels and in the interfascicular cambium. To investigate the role of DIM1 in cell wall formation, we generated loss-of-function and gain-of-function mutants. Disruption of the gene function caused
a dwarf phenotype with up to 38 and 23% reductions in total lignin and cellulose, respectively. Metabolite analysis revealed
a significant reduction in the levels of fructose, glucose and sucrose in the loss-of-function mutant compared to the wild
type control. The loss-of-function mutant also had a lower S/G lignin monomer ratio relative to wild type, but no changes
were detected in the gain-of-function mutant. Phloroglucinol and toluidine blue staining showed a size reduction of the vascular
apparatus with smaller and disintegrated xylem vessels in the inflorescence stem of the loss-of-function mutant. Taken together,
these data indicate a role for DIM1 in secondary cell wall formation. Moreover, this study demonstrated the potential role of BR hormones in modulating cell
wall structure and composition. 相似文献
123.
124.
Connecting the dots between PubMed abstracts 总被引:1,自引:0,他引:1
125.
Ghosh S Hossain MZ Borges M Goggins MG Ingersoll RG Eshleman JR Klein AP Kern SE 《PloS one》2012,7(4):e34426
5-Fluorouracil (5FU), a widely used chemotherapeutic drug, inhibits the DNA replicative enzyme, thymidylate synthase (Tyms). Prior studies implicated a VNTR (variable numbers of tandem repeats) polymorphism in the 5'-untranslated region (5'-UTR) of the TYMS gene as a determinant of Tyms expression in tumors and normal tissues and proposed that these VNTR genotypes could help decide fluoropyrimidine dosing. Clinical associations between 5FU-related toxicity and the TYMS VNTR were reported, however, results were inconsistent, suggesting that additional genetic variation in the TYMS gene might influence Tyms expression. We thus conducted a detailed genetic analysis of this region, defining new polymorphisms in this gene including mononucleotide (poly A:T) repeats and novel single nucleotide polymorphisms (SNPs) flanking the VNTR in the TYMS genetic region. Our haplotype analysis of this region used data from both established and novel genetic variants and found nine SNP haplotypes accounting for more than 90% of the studied population. We observed non-exclusive relationships between the VNTR and adjacent SNP haplotypes, such that each type of VNTR commonly occurred on several haplotype backgrounds. Our results confirmed the expectation that the VNTR alleles exhibit homoplasy and lack the common ancestry required for a reliable marker of a linked adjacent locus that might govern toxicity. We propose that it may be necessary in a clinical trial to assay multiple types of genetic polymorphisms in the TYMS region to meaningfully model linkage of genetic markers to 5FU-related toxicity. The presence of multiple long (up to 26 nt), polymorphic monothymidine repeats in the promoter region of the sole human thymidylate synthetic enzyme is intriguing. 相似文献
126.
Bernhard F. Benkel Amanda Smith Knud Christensen Razvan Anistoroaei Ye Zhang Christoph W. Sensen Hossain Farid Lyn Paterson Ronald M. Teather 《Genes & genomics.》2012,34(1):83-91
In this report we present the results of the analysis of approximately 2.7 Mb of genomic information for the American mink (Neovison vison) derived through BAC end sequencing. Our study, which encompasses approximately 1/1000th of the mink genome, suggests that simple sequence repeats (SSRs) are less common in the mink than in the human genome, whereas the average GC content of the mink genome is slightly higher than that of its human counterpart. The 2.7 Mb mink genomic dataset also contained 2,416 repeat elements (retroids and DNA transposons) occupying almost 31% of the sequence space. Among repeat elements, LINEs were over-represented and endogenous viruses (aka LTRs) under-represented in comparison to the human genome. Finally, we present a virtual map of the mink genome constructed with reference to the human and canine genome assemblies using a comparative genomics approach and incorporating over 200 mink BESs with unique hits to the human genome. 相似文献
127.
The anticancer drugs Adriamycin (ADR) and Daunomycin (DNM) of the anthracycline family are effective in treating a variety of cancers. Although their interactions with other cellular targets may play a role in the selective cytotoxicity of these drugs, it is generally believed that intercalation with DNA is essential for their activity. However, a relationship has not yet been established between intercalation and cellular processes leading to cytotoxicity. The present study was designed to investigate the relationship, if any, between intercalation and DNA strand breaks. ADR and DNM were observed to be strong intercalators of human genomic DNA by absorption and fluorimetric methods that were further substantiated by rise in thermal melting temperature. DNM is the better intercalator of the two, which is also evident from circular dichroic spectral changes. DNA strand breaks, considered to be an index of genotoxicity, was assayed by single cell gel electrophoresis (SCGE; comet assay). ADR and DNM induced equivalent genotoxicity in normal human lymphocytes at a clinically used dose, which was observed to be independent of intercalation efficiency though positively correlated to yield of reactive oxygen species. 相似文献
128.
Background
Drinking raw date palm sap is a risk factor for human Nipah virus (NiV) infection. Fruit bats, the natural reservoir of NiV, commonly contaminate raw sap with saliva by licking date palm’s sap producing surface. We evaluated four types of physical barriers that may prevent bats from contacting sap.Methods
During 2009, we used a crossover design and randomly selected 20 date palm sap producing trees and observed each tree for 2 nights: one night with a bamboo skirt intervention applied and one night without the intervention. During 2010, we selected 120 trees and randomly assigned four types of interventions to 15 trees each: bamboo, dhoincha (local plant), jute stick and polythene skirts covering the shaved part, sap stream, tap and collection pot. We enrolled the remaining 60 trees as controls. We used motion sensor activated infrared cameras to examine bat contact with sap.Results
During 2009 bats contacted date palm sap in 85% of observation nights when no intervention was used compared with 35% of nights when the intervention was used [p<0.001]. Bats were able to contact the sap when the skirt did not entirely cover the sap producing surface. Therefore, in 2010 we requested the sap harvesters to use larger skirts. During 2010 bats contacted date palm sap [2% vs. 83%, p<0.001] less frequently in trees protected with skirts compared to control trees. No bats contacted sap in trees with bamboo (p<0.001 compared to control), dhoincha skirt (p<0.001) or polythene covering (p<0.001), but bats did contact sap during one night (7%) with the jute stick skirt (p<0.001).Conclusion
Bamboo, dhoincha, jute stick and polythene skirts covering the sap producing areas of a tree effectively prevented bat-sap contact. Community interventions should promote applying these skirts to prevent occasional Nipah spillovers to human. 相似文献129.
Nusrat Homaira Stephen P. Luby William A. Petri Raija Vainionpaa Mustafizur Rahman Kamal Hossain Cynthia B. Snider Mahmudur Rahman A. S. M. Alamgir Farzina Zesmin Masud Alam Emily S. Gurley Rashid Uz Zaman Tasnim Azim Dean D. Erdman Alicia M. Fry Joseph Bresee Marc-Alain Widdowson Rashidul Haque Eduardo Azziz-Baumgartner 《PloS one》2012,7(2)
130.
Nadia Alam Monzur Hossain Md. Ibrahim Khalil Mohammed Moniruzzaman Siti Amrah Sulaiman Siew Hua Gan 《Phytochemistry Reviews》2012,11(1):97-112
Withania somnifera (L.) Dunal (Solanaceae), also known as ashwagandha, is an important medicinal plant that is widely used as a home remedy for several diseases in
the Indian subcontinent and other parts of the world. W. somnifera is a dietary supplement composed of various nutrients, polyphenols and alkaloids that have free radical scavenging capacity,
as well as other chemical constituents that possess anti-inflammatory, antitumor, anti-stress, antioxidant, immunomodulatory,
and rejuvenating properties. The mechanism of action for these properties are not fully understood. W. somnifera also appears to influence the endocrine, cardiopulmonary and central nervous systems. Toxicity studies reveal that W. somnifera can be used without side effects. The findings presented in this review are very encouraging and indicate that this herb
should be studied more extensively to confirm these results and to reveal other potential therapeutic effects. 相似文献