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991.
Mutations in mitochondrial DNA (mtDNA) are one of the most important causes of hearing loss. Of these, the homoplasmic A1555G and C1494T mutations at the highly conserved decoding site of the 12S rRNA gene are well documented as being associated with either aminoglycoside-induced or nonsyndromic hearing loss in many families worldwide. Moreover, five mutations associated with nonsyndromic hearing loss have been identified in the tRNASer(UCN) gene: A7445G, 7472insC, T7505C, T7510C, and T7511C. Other mtDNA mutations associated with deafness are mainly located in tRNA and protein-coding genes. Failures in mitochondrial tRNA metabolism or protein synthesis were observed from cybrid cells harboring these primary mutations, thereby causing the mitochondrial dysfunctions responsible for deafness. This review article provides a detailed summary of mtDNA mutations that have been reported in deafness and further discusses the molecular mechanisms of these mtDNA mutations in deafness expression. 相似文献
992.
Sandrine Lagarrigue Lisa Martin Farhad Hormozdiari Pierre-Fran?ois Roux Calvin Pan Atila van Nas Olivier Demeure Rita Cantor Anatole Ghazalpour Eleazar Eskin Aldons J. Lusis 《Genetics》2013,195(3):1157-1166
We report an analysis of allele-specific expression (ASE) and parent-of-origin expression in adult mouse liver using next generation sequencing (RNA-Seq) of reciprocal crosses of heterozygous F1 mice from the parental strains C57BL/6J and DBA/2J. We found a 60% overlap between genes exhibiting ASE and putative cis-acting expression quantitative trait loci (cis-eQTL) identified in an intercross between the same strains. We discuss the various biological and technical factors that contribute to the differences. We also identify genes exhibiting parental imprinting and complex expression patterns. Our study demonstrates the importance of biological replicates to limit the number of false positives with RNA-Seq data. 相似文献
993.
Jinhe Pan Neale S. Mason Manik L. Debnath Chester A. Mathis William E. Klunk Kuo-Shyan Lin 《Bioorganic & medicinal chemistry letters》2013,23(6):1720-1726
To continue our efforts toward the development of 99mTc PiB analogs, we have synthesized 24 neutral and lipophilic Re (as a surrogate of 99mTc) 2-arylbenzothiazoles, and explored their structure–activity relationship for binding to Aβ1–40 fibrils. These Re complexes were designed and synthesized via the integrated approach, so their 99mTc analogs would have a greater chance of crossing the blood–brain barrier. While the lipophilicities (log PC18 = 1.59–3.53) of these Re 2-arylbenzothiazoles were all within suitable range, their binding affinities (Ki = 30–617 nM) to Aβ1–40 fibrils varied widely depending on the selection and integration of the tetradentate chelator into the 2-phenylbenzothiazole pharmacophore. For potential clinical applications, further refinement to obtain Re 2-arylbenzothiazoles with better binding affinities (<10 nM) will likely be needed. The integrated approach reported here to generate compact, neutral and lipophilic Re 2-arylbenzothiazoles could be applied to other potent pharmacophores as well to convert other current Aβ PET tracers to their 99mTc analogs for more widespread application via the use of SPECT scanners. 相似文献
994.
Xiao-Chao Huang Meng Wang Ying-Ming Pan Xiao-Yan Tian Heng-Shan Wang Ye Zhang 《Bioorganic & medicinal chemistry letters》2013,23(19):5283-5289
A series of novel α-aminophosphonate derivatives containing DHA structure were designed and synthesized as antitumor agents. In vitro antitumor activities of these compounds against the NCI-H460 (human lung cancer cell), A549 (human lung adenocarcinoma cell), HepG2 (human liver cancer cell) and SKOV3 (human ovarian cancer cell) human cancer cell lines were evaluated and compared with commercial anticancer drug 5-fluorouracil (5-FU), employing standard MTT assay. The pharmacological screening results revealed that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most demonstrated more potent inhibitory activities compared with the commercial anticancer drug 5-FU. The action mechanism of representative compound 7c was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which indicated that the compound can induce cell apoptosis in NCI-H460 cells. Cell cycle analysis showed that compound 7c mainly arrested NCI-H460 cells in G1 stage. 相似文献
995.
Jiachuan Pan Fangchao Song Dacheng Ren 《Bioorganic & medicinal chemistry letters》2013,23(16):4648-4651
Pseudomonas aeruginosa is a major pathogen causing chronic pulmonary infections; for example, 80% of cystic fibrosis patients get infected by this bacterium as the disease progresses. Such chronic infections are challenging because P. aeruginosa exhibits high-level tolerance to antibiotics by forming biofilms (multicellular structures attached to surfaces), by entering dormancy and forming antibiotic tolerant persister cells, and by conversion to the mucoid phenotype. Recently, we reported that a synthetic quorum sensing inhibitor, (Z)-4-bromo-5-(bromomethylene)-3-methylfuran-2(5H)-one (BF8), can sensitize both planktonic and biofilm-associated persister cells of P. aeruginosa PAO1 to antibiotics at the concentrations non-inhibitory to its growth. In this study, we further characterized the effects of this compound on the mucoid strain P. aeruginosa PDO300. BF8 was found to reduce persistence during the growth of PDO300 and effectively kill the persister cells isolated from PDO300 cultures. In addition to planktonic cells, BF8 was also found to inhibit biofilm formation of PDO300 and reduce associated persistence. These findings broaden the activities of this class of compounds and indicate that BF8 also has other targets in P. aeruginosa in addition to quorum sensing. 相似文献
996.
Simeon Bowers Ying-zi Xu Shendong Yuan Gary D. Probst Roy K. Hom Wayman Chan Andrei W. Konradi Hing L. Sham Yong L. Zhu Paul Beroza Hu Pan Eric Brecht Nanhua Yao Julie Lougheed Danny Tam Zhao Ren Lany Ruslim Michael P. Bova Dean R. Artis 《Bioorganic & medicinal chemistry letters》2013,23(7):2181-2186
The structure–activity relationship of a series of dihydroisoquinoline BACE-1 inhibitors is described. Application of structure-based design to screening hit 1 yielded sub-micromolar inhibitors. Replacement of the carboxylic acid of 1 was guided by X-ray crystallography, which allowed the replacement of a key water-mediated hydrogen bond. This work culminated in compounds such as 31, which possess good BACE-1 potency, excellent permeability and a low P-gp efflux ratio. 相似文献
997.
998.
Xiaoyan Pan Fang Wang Yanmin Zhang Hongping Gao Zhigang Hu Sicen Wang Jie Zhang 《Bioorganic & medicinal chemistry》2013,21(9):2527-2534
A novel class of Nilotinib derivatives, B1–B20, were synthesized in high yields using various substituted anilines. All the title compounds were evaluated for their inhibitory activities against Bcr–Abl and antiproliferative effects on human leukemia cell (K562). The pharmacological results indicated that some compounds exhibited promising anticancer activity. In particular, compound B14 containing tertiary amine side chain exhibited Bcr–Abl inhibitory activity similar to that of Nilotinib. It was suggested that the introduction of the tertiary amine moiety could improve Bcr–Abl inhibitory activity and antitumor effects. 相似文献
999.
1000.
描述了产自内蒙古二连盆地呼和勃尔和地区始新世壮鼠类化石,包括呼和勃尔和剖面伊尔丁曼哈组底部的Asiomys dawsoni以及努和廷勃尔和剖面阿山头组底部的Ischyromyidae gen.et sp.indet.。其中Asiomys与其他壮鼠类的区别在于其下颌厚、高;咬肌窝明显、前缘宽,并有较明显的结节;P4无次尖、M1和M2次尖小;后小尖2个;dp4有明显的下次脊、p4无下次脊;下臼齿下原尖后棱长短不一、下次尖与下后齿带相连、下外脊完整、下次脊短。Asiomys的下颌特征与Paramys delicatus相似,门齿釉质层、上臼齿次尖、下臼齿下次脊等结构特征与北美中始新世的壮鼠类相近,与亚洲已知的壮鼠类差别较大。因此,Asiomys是中始新世亚洲与北美大陆哺乳动物之间交流的又一佐证。 相似文献