全文获取类型
收费全文 | 1980篇 |
免费 | 142篇 |
国内免费 | 3篇 |
出版年
2021年 | 14篇 |
2020年 | 10篇 |
2019年 | 14篇 |
2018年 | 23篇 |
2017年 | 20篇 |
2016年 | 35篇 |
2015年 | 56篇 |
2014年 | 65篇 |
2013年 | 96篇 |
2012年 | 94篇 |
2011年 | 98篇 |
2010年 | 61篇 |
2009年 | 55篇 |
2008年 | 89篇 |
2007年 | 109篇 |
2006年 | 111篇 |
2005年 | 91篇 |
2004年 | 103篇 |
2003年 | 99篇 |
2002年 | 77篇 |
2001年 | 77篇 |
2000年 | 63篇 |
1999年 | 56篇 |
1998年 | 23篇 |
1997年 | 19篇 |
1996年 | 18篇 |
1995年 | 19篇 |
1994年 | 12篇 |
1993年 | 11篇 |
1992年 | 57篇 |
1991年 | 44篇 |
1990年 | 42篇 |
1989年 | 34篇 |
1988年 | 32篇 |
1987年 | 30篇 |
1986年 | 33篇 |
1985年 | 30篇 |
1984年 | 21篇 |
1983年 | 15篇 |
1982年 | 13篇 |
1981年 | 14篇 |
1980年 | 16篇 |
1979年 | 20篇 |
1978年 | 15篇 |
1977年 | 16篇 |
1976年 | 9篇 |
1975年 | 8篇 |
1974年 | 12篇 |
1970年 | 7篇 |
1968年 | 6篇 |
排序方式: 共有2125条查询结果,搜索用时 78 毫秒
991.
Taisuke Katoh Yoshihide Tomata Masaki Setoh Satoshi Sasaki Takafumi Takai Yayoi Yoshitomi Tomoya Yukawa Hideyuki Nakagawa Shoji Fukumoto Tetsuya Tsukamoto Yoshihisa Nakada 《Bioorganic & medicinal chemistry letters》2017,27(11):2497-2501
We previously reported a facile preparation method of 3-substituted-2,6-difluoropyridines, which were easily converted to 2,3,6-trisubstituted pyridines by nucleophilic aromatic substitution with good regioselectivity and yield. In this study, we demonstrate the synthetic utility of 3-substituted-2,6-difluoropyridines in drug discovery via their application in the synthesis of various 2,3,6-trisubstituted pyridines, including macrocyclic derivatives, as novel protein kinase C theta inhibitors in a moderate to good yield. This synthetic approach is useful for the preparation of 2,3,6-trisubstituted pyridines, which are a popular scaffold for drug candidates and biologically attractive compounds. 相似文献
992.
Chiaki I. Yasuda Masaya Otoda Reiko Nakano Yuki Takiya Tsunenori Koga 《Ecological Research》2017,32(3):347-357
Sexual size dimorphism is a common phenomenon in the animal kingdom, and its seasonal change has been reported in some species that possess traits dimorphic only in males and specialized for male mating success. However, few studies have examined seasonal change in sexual dimorphism of traits possessed by both sexes. Here, we examined the reproductive biology of the hermit crab Pagurus minutus, at a sandflat in the Waka River estuary, Japan, with special reference to seasonal changes in sexual dimorphism of the large claw (major cheliped) size by conducting population and precopulatory guarding-pair sampling. Previous investigation demonstrated that the major cheliped is used as a weapon, and its size, more than body size, determines the winner in male–male contests of this species. We found ovigerous females from November to April, peaking in January, when 80% of females were ovigerous. Sexual size dimorphism of the major cheliped was observed; the degree of dimorphism increased in the reproductive season, when only males possessed an enlarged major cheliped. In addition, in the reproductive season, precopulatory guarding males had a larger body and larger relative size of the major cheliped than did solitary males, although the major cheliped size in guarding males seemed to reach an upper limit. These results suggest that seasonal change in sexual dimorphism of the major cheliped size in P. minutus strongly reflects sexual selection favoring the development of this natural weaponry, and that the degree of the dimorphism might be limited through natural selection. 相似文献
993.
Daisuke Yasuda Akihiro Yuasa Rika Obata Mao Nakajima Kyoko Takahashi Tomoyuki Ohe Yoshinobu Ichimura Masaaki Komatsu Masayuki Yamamoto Riyo Imamura Hirotatsu Kojima Takayoshi Okabe Tetsuo Nagano Tadahiko Mashino 《Bioorganic & medicinal chemistry letters》2017,27(22):5006-5009
The Keap1-Nrf2 system is an attractive target for drug discovery regarding various unmet medical needs. Only covalent inhibitors for protein-protein interaction (PPI) between Keap1 and Nrf2 to activate Nrf2 have been approved or are under clinical trials, but such electrophilic compounds lack selectivity. Therefore, specific non-covalent Keap1-Nrf2 PPI inhibitors are expected to be safer Nrf2 activators. We found a novel class of non-covalent Keap1-Nrf2 PPI inhibitor that has a benzo[g]indole skeleton and an indole-3-hydroxamic acid moiety and that exhibits significant PPI inhibitory activity. Additionally, the benzo[g]indole-3-carbohydrazide derivatives were newly prepared. The benzo[g]indole derivatives showed a stronger Keap1-Nrf2 PPI inhibitory activity than Cpd16, a previously reported non-covalent PPI inhibitor. Moreover, most of the PPI inhibitors showed a high metabolic stability in a human microsome system with a low cytotoxicity against HepG2 cell lines, which suggests that novel benzo[g]indole-type Keap1-Nrf2 PPI inhibitors are expected to be biological tools or lead compounds for Nrf2 activators. 相似文献
994.
Bharat Lagu Arthur F. Kluge Ross A. Fredenburg Effie Tozzo Ramesh S. Senaiar Mahaboobi Jaleel Sunil K. Panigrahi Nirbhay K. Tiwari Narasimha R. Krishnamurthy Taisuke Takahashi Michael A. Patane 《Bioorganic & medicinal chemistry letters》2017,27(23):5230-5234
Optimization of benzamide PPARδ modulator 1 led to (E)-6-(2-((4-(furan-2-yl)-N-methylbenzamido)methyl)phenoxy)-4-methylhex-4-enoic acid (18), a potent selective PPARδ modulator with significantly improved exposure in multiple species following oral administration. 相似文献
995.
Etsuko Tsubota Toshihiro Yasuda Reiko Iida 《Comparative biochemistry and physiology. Part D, Genomics & proteomics》2008,3(1):91
The aim of this study was to identify genes expressed in an age-dependent manner in mouse (Mus musculus) liver. To search for age-dependently expressed genes, we used a fluorescence differential display–PCR (FDD–PCR) technique on total RNA extracted from mouse livers collected at seven different developmental stages. All differentially expressed cDNAs detected by FDD–PCR were reamplified, subcloned and sequenced, and six genes were confirmed to show age-dependent expression by quantitative real-time PCR analysis. Nucleotide sequence analyses showed that four of them had high homology with known genes (mitochondrial DNA, cytosolic aldehyde dehydrogenase, cell division cycle 2-like 5 and complement component 8 alpha polypeptide), and two with expressed sequence tags of unknown genes. The FDD–PCR technique was effective for detecting novel age-dependently expressed genes, and also for newly characterizing individual expression patterns of known genes. The age-dependent expression patterns of known genes revealed in this study may provide an opportunity to investigate the unknown physiological roles of the proteins they encode. 相似文献
996.
Presence of side-population cells in an immortalized nontumorigenic human liver epithelial cell line
Yamazaki T Enosawa S Tsukiyama T Tokiwa T 《In vitro cellular & developmental biology. Animal》2008,44(1-2):6-9
Side-population (SP) cells have been shown to be highly enriched stem cells. We investigated whether an immortalized, nontumorigenic
human liver cell line, THLE-5b, contains SP cells. Flow cytometry analysis after Hoechst 33342 staining demonstrated that
the THLE-5b line contained a small component of SP cells. These SP cells were essentially eliminated by treatment with verapamil
and expressed higher levels of ABCG2 mRNA than non-SP cells. In addition, the level of these SP cells detected by Hoechst
33342 staining was affected by the experimental conditions including the incubation medium. This is the first report of the
presence of SP cells in the immortalized, nontumorigenic human liver cell line. 相似文献
997.
998.
999.
Nina Yasuda Satoshi Nagai Chunlian Lian Masami Hamaguchi Takeshi Hayashibara Kazuo Nadaoka 《Conservation Genetics》2008,9(4):1011-1013
We isolated 11 polymorphic microsatellites from blue coral (Heliopora coerulea), whose conservation and management are of great concern. The number of alleles ranged from 3 to 20 with an average of 5.5,
and the observed and expected heterozygosities ranged from 0.115 to 0.833 and from 0.371 to 0.915, respectively. These loci
are useful for conservation genetics in H. coerulea populations. 相似文献
1000.
Inui M Suda M Kimura S Yasuda K Suzuki H Toda H Yamamoto S Okino S Suzuki N Yukawa H 《Applied microbiology and biotechnology》2008,77(6):1305-1316
A recombinant butanol pathway composed of Clostridium acetobutylicum ATCC 824 genes, thiL, hbd, crt, bcd-etfB-etfA, and adhe1 (or adhe) coding for acetyl-CoA acetyltransferase (THL), β-hydroxybutyryl-CoA dehydrogenase (HBD), 3-hydroxybutyryl-CoA dehydratase
(CRT), butyryl-CoA dehydrogenase (BCD), butyraldehyde dehydrogenase (BYDH), and butanol dehydrogenase (BDH), under the tac promoter control was constructed and was introduced into Escherichia coli. The functional expression of these six enzymes was proved by demonstrating the corresponding enzyme activities using spectrophotometric,
high performance liquid chromatography and gas chromatography analyses. The BCD activity, which was not detected in E. coli previously, was shown in the present study by performing the procedure from cell extract preparation to activity measurement
under anaerobic condition. Moreover, the etfA and etfB co-expression was found to be essential for the BCD activity. In the case of BYDH activity, the adhe gene product was shown to have higher specificity towards butyryl-CoA compared to the adhe1 product. Butanol production from glucose was achieved by the highly concentrated cells of the butanologenic E. coli strains, BUT1 with adhe1 and BUT2 with adhe, under anaerobic condition, and the BUT1 and BUT2 strains were shown to produce 4 and 16-mM butanol with 6- and 1-mM butyrate
as a byproduct, respectively. This study reports the novel butanol production by an aerobically pregrown microorganism possessing
the genes of a strict anaerobe, Clostridium acetobutylicum. 相似文献