全文获取类型
收费全文 | 684篇 |
免费 | 34篇 |
出版年
2023年 | 2篇 |
2022年 | 7篇 |
2021年 | 18篇 |
2020年 | 8篇 |
2019年 | 9篇 |
2018年 | 21篇 |
2017年 | 14篇 |
2016年 | 18篇 |
2015年 | 20篇 |
2014年 | 35篇 |
2013年 | 67篇 |
2012年 | 60篇 |
2011年 | 53篇 |
2010年 | 30篇 |
2009年 | 23篇 |
2008年 | 43篇 |
2007年 | 43篇 |
2006年 | 46篇 |
2005年 | 38篇 |
2004年 | 25篇 |
2003年 | 26篇 |
2002年 | 32篇 |
2001年 | 4篇 |
2000年 | 3篇 |
1999年 | 5篇 |
1998年 | 4篇 |
1997年 | 6篇 |
1996年 | 16篇 |
1995年 | 6篇 |
1994年 | 3篇 |
1990年 | 3篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 5篇 |
1981年 | 8篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1974年 | 2篇 |
排序方式: 共有718条查询结果,搜索用时 31 毫秒
91.
S. Rajesh Eiichi Ami Tomoya Kotake Tooru Kimura Yoshio Hayashi Yoshiaki Kiso 《Bioorganic & medicinal chemistry letters》2002,12(24):4567-3617
Z- and Fmoc-L-tetrahydrofuranylglycines have been obtained from L-vinylglycine through dipolar cycloaddition reaction, and its Fmoc derivative has been applied in the synthesis of modified S9 and S10 substrates of HIV-1 protease. These compounds mostly acted as strong inhibitors, rather than substrates, of the protease, probably due to the favourable interactions of the tetrahydrofuranylglycine moiety at the S(2) site. 相似文献
92.
Three clones of dispersed repetitive sequences (MCS-26a, JA-5and JB-7) were isolated from a library of PCR products amplifiedfrom Citrus DNA using primers complementary to the minisatellitecore sequences. Distribution of these repetitive sequences inthe genomic DNA was highly variable among members of the Rutaceaefamily studied here. MCS-26a was specifically amplified in thesubfamily Aurantioideae, but not in other subfamilies of theRutaceae. Different levels of JA-5 amplification were observedamong genera in the subfamily Aurantioideae. JB-7 was widelydetected throughout the Rutaceae. These data suggest that thethree repeated sequences analysed in this study were amplifiedat different stages in the evolution of Rutaceae and that theyare useful for systematic studies of the Rutaceae. In addition,the repetitive sequences displayed a high level of restrictionfragment length polymorphism (RFLP) among Citrus species andtheir relatives, suggesting that they serve as hot spots forchanges in the genome after amplification. Copyright 2001 Annalsof Botany Company Citrus, Rutaceae, repeated sequences, DNA fingerprinting, RFLP 相似文献
93.
Toshio Atsumi Toshitsugu Fukumaru Tomoya Ogawa Masanao Matsui 《Bioscience, biotechnology, and biochemistry》2013,77(11):2621-2626
A novel synthesis of N-acetyllincosamine derivatives (3) and (14) was accomplished. 相似文献
94.
Mitsunori Kono Tsuneo Oda Michiko Tawada Takashi Imada Yoshihiro Banno Naohiro Taya Tetsuji Kawamoto Hidekazu Tokuhara Yoshihide Tomata Naoki Ishii Atsuko Ochida Yoshiyuki Fukase Tomoya Yukawa Shoji Fukumoto Hiroyuki Watanabe Keiko Uga Akira Shibata Hideyuki Nakagawa Satoshi Yamamoto 《Bioorganic & medicinal chemistry》2018,26(2):470-482
A series of tetrahydroisoquinoline derivatives were designed, synthesized, and evaluated for their potential as novel orally efficacious retinoic acid receptor-related orphan receptor-gamma t (RORγt) inverse agonists for the treatment of Th17-driven autoimmune diseases. We carried out cyclization of the phenylglycinamide core by structure-based drug design and successfully identified a tetrahydroisoquinoline carboxylic acid derivative 14 with good biochemical binding and cellular reporter activity. Interestingly, the combination of a carboxylic acid tether and a central fused bicyclic ring was crucial for optimizing PK properties, and the compound 14 showed significantly improved PK profile. Successive optimization of the carboxylate tether led to the discovery of compound 15 with increased inverse agonistic activity and an excellent PK profile. Oral treatment of mice with compound 15 robustly and dose-dependently inhibited IL-17A production in an IL23-induced gene expression assay. 相似文献
95.
Takuma Inai Tomoya Takabayashi Mutsuaki Edama Masayoshi Kubo 《Biomedical engineering online》2018,17(1):177
Background
Sit-to-stand movements are a necessary part of daily life, and excessive mechanical stress on the articular cartilage has been reported to encourage the progression of osteoarthritis. Although a change in hip joint angle at seat-off may affect hip joint contact force during a sit-to-stand movement, the effect is unclear. This study aimed to examine the effect of the hip joint angle at seat-off on the hip joint contact force during a sit-to-stand movement by using a computer simulation.Methods
A musculoskeletal model was created for the computer simulation, and eight muscles were attached to each lower limb. Various sit-to-stand movements were generated using parameters (e.g., seat height and time from seat-off to standing posture) reported by previous studies. The hip joint contact force for each sit-to-stand movement was calculated. Furthermore, the effect of the hip joint angle at seat-off on the hip joint contact force during the sit-to-stand movement was examined. In this study, as the changes to the musculoskeletal model parameters affect the hip joint contact force, a sensitivity analysis was conducted.Results and conclusions
The hip joint contact force during the sit-to-stand movement increased approximately linearly as the hip flexion angle at the seat-off increased. Moreover, the normal sit-to-stand movement and the sit-to-stand movement yielding a minimum hip joint contact force were approximately equivalent. The effect of the changes to the musculoskeletal model parameters on the main findings of this study was minimal. Thus, the main findings are robust and may help prevent the progression of hip osteoarthritis by decreasing mechanical stress, which will be explored in future studies.96.
Natsumi Takei Takuma Nakamura Shohei Kawamura Yuki Takada Yui Satoh Atsushi P. Kimura Tomoya Kotani 《Biological procedures online》2018,20(1):6
Background
Subcellular localization of coding and non-coding RNAs has emerged as major regulatory mechanisms of gene expression in various cell types and many organisms. However, techniques that enable detection of the subcellular distribution of these RNAs with high sensitivity and high resolution remain limited, particularly in vertebrate adult tissues and organs. In this study, we examined the expression and localization of mRNAs encoding Pou5f1/Oct4, Mos, Cyclin B1 and Deleted in Azoospermia-like (Dazl) in zebrafish and mouse ovaries by combining tyramide signal amplification (TSA)-based in situ hybridization with paraffin sections which can preserve cell morphology of tissues and organs at subcellular levels. In addition, the distribution of a long non-coding RNA (lncRNA), lncRNA-HSVIII, in mouse testes was examined by the same method.Results
The mRNAs encoding Mos, Cyclin B1 and Dazl were found to assemble into distinct granules that were distributed in different subcellular regions of zebrafish and mouse oocytes, suggesting conserved and specific regulations of these mRNAs. The lncRNA-HSVIII was first detected in the nucleus of spermatocytes at prophase I of the meiotic cell cycle and was then found in the cytoplasm of round spermatids, revealing expression patterns of lncRNA during germ cell development. Collectively, the in situ hybridization method demonstrated in this study achieved the detection and comparison of precise distribution patterns of coding and non-coding RNAs at subcellular levels in single cells of adult tissues and organs.Conclusions
This high-sensitivity and high-resolution in situ hybridization is applicable to many vertebrate species and to various tissues and organs and will be useful for studies on the subcellular regulation of gene expression at the level of RNA localization.97.
98.
Melody Cabrera Ospino Hisaya Kojima Tomohiro Watanabe Tomoya Iwata Manabu Fukui 《Limnology》2018,19(2):177-183
Anaerobic arsenite oxidation is potentially important but the least understood process in the arsenic cycle. The catalytic subunit of the key enzyme for anaerobic arsenite oxidation is encoded by the arxA gene. In this study, a novel primer pair for the arxA gene was designed to detect diverse sequences of this notable gene. Further modification of the designed primer was made by adding extra bases to its 5′- end. This modification made it possible to analyze the PCR products with TA cloning, which provides higher throughput of investigations. With the combination of modified primer pair and TA cloning, diverse arxA gene sequences were effectively obtained from samples of lake water, spring water, and hot spring microbial mat. The sequences detected in the samples characterized by low salinity and nearly neutral pH were phylogenetically distinct from the majority of previously known arxA genes, found in the genome of alkaliphiles and halophiles. 相似文献
99.
100.
Masahiko Yamamoto Takeshi Yasuda Kiyoshi Hayasaka A. Ohnishi Hiroo Yoshikawa Takehiko Yanagihara Tohru Ikegami Tatsunori Yamamoto Hirofumi Ohashi Tomoya Nishimura Terunori Mitsuma Hidenori Kiyosawa Phillip F. Chance G. Sobue 《Human genetics》1997,100(2):151-154
We have used human β2 and β4 cDNA probes to map the genes encoding two isoforms of the regulatory β subunit of voltage-activated
Ca2+ channels, viz. CACNB2 (β2) and CACNB4 (β4), to human chromosomes 10p12 and 2q22-q23, respectively, by fluorescence in situ
hybridization. The gene encoding the β2 protein, first described as a Lambert-Eaton myasthenic syndrome (LEMS) antigen in
humans, is found close to a region that undergoes chromosome rearrangements in small cell lung cancer, which occurs in association
with LEMS. CACNB2 (β2) and CACNB4 (β4) genes are members of the ion-channel gene superfamily and it should now be possible
to examine their loci by linkage analysis of ion-channel-related disorders. To date, no such disease-related gene has been
assigned to 10p12 and 2q22-q23.
Received: 5 February 1997 / Accepted: 4 April 1997 相似文献