全文获取类型
收费全文 | 3254篇 |
免费 | 199篇 |
出版年
2023年 | 12篇 |
2022年 | 39篇 |
2021年 | 65篇 |
2020年 | 36篇 |
2019年 | 46篇 |
2018年 | 79篇 |
2017年 | 56篇 |
2016年 | 91篇 |
2015年 | 145篇 |
2014年 | 145篇 |
2013年 | 260篇 |
2012年 | 238篇 |
2011年 | 247篇 |
2010年 | 138篇 |
2009年 | 137篇 |
2008年 | 202篇 |
2007年 | 198篇 |
2006年 | 174篇 |
2005年 | 163篇 |
2004年 | 173篇 |
2003年 | 138篇 |
2002年 | 143篇 |
2001年 | 37篇 |
2000年 | 39篇 |
1999年 | 36篇 |
1998年 | 38篇 |
1997年 | 33篇 |
1996年 | 29篇 |
1995年 | 24篇 |
1994年 | 21篇 |
1993年 | 22篇 |
1992年 | 30篇 |
1991年 | 38篇 |
1990年 | 27篇 |
1989年 | 30篇 |
1988年 | 17篇 |
1987年 | 12篇 |
1986年 | 12篇 |
1985年 | 16篇 |
1984年 | 14篇 |
1983年 | 6篇 |
1981年 | 5篇 |
1980年 | 6篇 |
1979年 | 6篇 |
1978年 | 6篇 |
1972年 | 4篇 |
1970年 | 2篇 |
1968年 | 2篇 |
1967年 | 2篇 |
1966年 | 2篇 |
排序方式: 共有3453条查询结果,搜索用时 968 毫秒
101.
Osamu Takaku Hiroki Haraguchi Shozo Toda Keiichiro Fuwa 《Bioscience, biotechnology, and biochemistry》2013,77(12):2373-2381
Nucleotides, 5′-AMP, 5′-GMP, 5′-UMP, 5′-CMP and 5′-TMP, in D2O solution have been investigated by proton magnetic resonance spectroscopy. The concentration and the pD dependences of the proton chemical shifts of the nucleotides have been examined in detail. These results indicate that intermolecular association of vertical stacking of the base rings and intramolecular association between base protons and ionized phosphate group occur in solution. The effects of the temperature and lithium ion on 5′-AMP and 5′-UMP have been also investigated. The increase of temperature causes to reduce the intramolecular association for 5′-UMP and the both intra- and intermolecular association for 5′-AMP. Lithium ion reduces the intramolecular association for both 5′-AMP and 5′-UMP, and at the same time promotes the intermolecular one for the former. This can be interpreted by the ion-pair formation of lithium ion with the ionized phosphate group. 相似文献
102.
β-Xylosidase was purified 662 fold from a culture filtrate by ammonium sulfate fractionation, gel filtration on Biogel P-100, DEAE-Sephadex chromatography, and gel filtration on Sephadex G-200. With isoelectric focusing, the purified β-xylosidase found to be homogeneous on SDS (sodium dodecyl sulfate) polyacrylamide gel electrophoresis. The molecular weight was estimated by gel filtration to be 240,000, and 116,000 by SDS polyacrylamide gel electrophoresis. The purified β-xylosidase had an isoelectric point at pH 3.25, and contained 4% carbohydrate residue. The optimum pH was found to be in the range of 4.5 ~ 5, and the optimum temperature was 55°C. The enzyme activity was inhibited by Hg2 +, SDS, and N-bromosuccinimide at a concentration of 1 × 10?3 m, and also p-chloromercuribenzoate at a concentration of 1 × 10?4m. The purified enzyme hydrolyzed phenyl β-d-xyloside (ko = 302.6 sec?1),β-nitrophenyl β-d-xyloside (ko = 438.9 sec?1), o-nitrophenyl β-d-xyloside (ko = 431.0 sec?1), p-chlorophenyl β-d-xyloside (ko = 207.9 sec?1), o-chlorophenyl β-d-xyloside (ko = 211.8 sec?1), β-methylphenyl β-d-xyloside ko = 96.5 sec?1), o-methylphenyl β-d-xyloside (ko = 83.1 sec?1), p-methoxyphenyl β-d-xyloside (ko = 99.3 sec?1), o-methoxyphenyl β-d-xyloside (ko= 100.0 sec?1), xylobiose (ko = 992A sec?1), xylotriose (ko = 1321.9 sec?1), xylotetraose (ko = 7S9.1 sec?1) and xylopentaose (ko = 508.0 sec?1). On enzymic hydrolysis of phenyl β-d-xyloside, the reaction product was found to be β-d-xylose with retention of the configuration. The purified β-xylosidase was practically free of a-xylosidase and β-glucosidase activities. 相似文献
103.
Hiroki Hayase Nobumoto Watanabe Chung Liang Lim Toshihiko Nogawa Keisuke Komatsuya Kiyoshi Kita 《Bioscience, biotechnology, and biochemistry》2013,77(4):633-635
Quinomycin A and its derivatives were identified as potent antimalarial (Plasmodium falciparum) agents in a screen of the RIKEN NPDepo chemical library. IC50 values of quinomycin A and UK-63,598 were approximately 100 times lower than that of the antimalarial drug chloroquine. This activity was mitigated by the addition of plasmid DNA, suggesting that these compounds act against parasites by intercalating into their DNA. 相似文献
104.
Sayaka Moriwaki Hiroki Murakami Nobuyuki Takahashi Taku Uemura Keiko Taketani Shohei Hoshino 《Bioscience, biotechnology, and biochemistry》2013,77(7):1231-1236
Yamogenin is a diastereomer of diosgenin, which we have identified as the compound responsible for the anti-hyperlipidemic effect of fenugreek. Here, we examined the effects of yamogenin on the accumulation of triacylglyceride (TG) in hepatocytes, because yamogenin is also contained in fenugreek. It was demonstrated that yamogenin also inhibited TG accumulation in HepG2 hepatocytes and suppressed the mRNA expression of fatty acid synthesis-related genes such as fatty acid synthase and sterol response element-binding protein-1c. Indeed, yamogenin also antagonized the activation of the liver X receptor (LXR) in luciferase ligand assay similar to diosgenin. However, yamogenin could not exert such effects in the presence of T0901713, a potent agonist of LXR. These findings indicate that the effects of yamogenin on TG accumulation would be weaker than those of diosgenin, suggesting that the structural difference between yamogenin and diosgenin would be important for the inhibition of LXR activation. 相似文献
105.
Rishni Masimbula Katsunari Oki Hiroki Shibata Hisashi Osawa Norio Kondo 《Bioscience, biotechnology, and biochemistry》2013,77(9):1650-1654
ABSTRACTThe pathogenic fungi Gibberella fujikuroi and Fusarium commune produce jasmonic acid. The application of volatile deuterium-labeled methyl jasmonate increased the amount of nonlabeled JA present in G. fujikuroi and F. commune. These results indicate that the fungi have the ability to react with airborne methyl jasmonate in a manner similar to a plant. 相似文献
106.
Ki-Sung Kim Yuichiro Arima Taro Kitazawa Koichi Nishiyama Rieko Asai Yasunobu Uchijima Takahiro Sato Giovanni Levi Sachiko Kitanaka Takashi Igarashi Yukiko Kurihara Hiroki Kurihara 《Mechanisms of development》2013,130(11-12):553-566
Endothelin-1 (Edn1), originally identified as a vasoconstrictor peptide, is involved in the development of cranial/cardiac neural crest-derived tissues and organs. In craniofacial development, Edn1 binds to Endothelin type-A receptor (Ednra) to induce homeobox genes Dlx5/Dlx6 and determines the mandibular identity in the first pharyngeal arch. However, it remains unsolved whether this pathway is also critical for pharyngeal arch artery development to form thoracic arteries. Here, we show that the Edn1/Ednra signaling is involved in pharyngeal artery development by controlling the fate of neural crest cells through a Dlx5/Dlx6-independent mechanism. Edn1 and Ednra knock-out mice demonstrate abnormalities in pharyngeal arch artery patterning, which include persistent first and second pharyngeal arteries, resulting in additional branches from common carotid arteries. Neural crest cell labeling with Wnt1-Cre transgene and immunostaining for smooth muscle cell markers revealed that neural crest cells abnormally differentiate into smooth muscle cells at the first and second pharyngeal arteries of Ednra knock-out embryos. By contrast, Dlx5/Dlx6 knockout little affect the development of pharyngeal arch arteries and coronary arteries, the latter of which is also contributed by neural crest cells through an Edn-dependent mechanism. These findings indicate that the Edn1/Ednra signaling regulates neural crest differentiation to ensure the proper patterning of pharyngeal arch arteries, which is independent of the regional identification of the pharyngeal arches along the dorsoventral axis mediated by Dlx5/Dlx6. 相似文献
107.
Yadav Sapkota Sunita Ghosh Raymond Lai Bradley P. Coe Carol E. Cass Yutaka Yasui John R. Mackey Sambasivarao Damaraju 《PloS one》2013,8(1)
Breast cancer recurrence (BCR) is a common treatment outcome despite curative-intent primary treatment of non-metastatic breast cancer. Currently used prognostic and predictive factors utilize tumor-based markers, and are not optimal determinants of risk of BCR. Germline-based copy number aberrations (CNAs) have not been evaluated as determinants of predisposition to experience BCR. In this study, we accessed germline DNA from 369 female breast cancer subjects who received curative-intent primary treatment following diagnosis. Of these, 155 experienced BCR and 214 did not, after a median duration of follow up after breast cancer diagnosis of 6.35 years (range = 0.60–21.78) and 8.60 years (range = 3.08–13.57), respectively. Whole genome CNA genotyping was performed on the Affymetrix SNP array 6.0 platform. CNAs were identified using the SNP-Fast Adaptive States Segmentation Technique 2 algorithm implemented in Nexus Copy Number 6.0. Six samples were removed due to poor quality scores, leaving 363 samples for further analysis. We identified 18,561 CNAs with ≥1 kb as a predefined cut-off for observed aberrations. Univariate survival analyses (log-rank tests) identified seven CNAs (two copy number gains and five copy neutral-loss of heterozygosities, CN-LOHs) showing significant differences (P<2.01×10−5) in recurrence-free survival (RFS) probabilities with and without CNAs.We also observed three additional but distinct CN-LOHs showing significant differences in RFS probabilities (P<2.86×10−5) when analyses were restricted to stratified cases (luminal A, n = 208) only. After adjusting for tumor stage and grade in multivariate analyses (Cox proportional hazards models), all the CNAs remained strongly associated with the phenotype of BCR. Of these, we confirmed three CNAs at 17q11.2, 11q13.1 and 6q24.1 in representative samples using independent genotyping platforms. Our results suggest further investigations on the potential use of germline DNA variations as prognostic markers in cancer-associated phenotypes. 相似文献
108.
Satoshi Yamamoto Kenji Minami Keiichi Fukaya Kohji Takahashi Hideki Sawada Hiroaki Murakami Satsuki Tsuji Hiroki Hashizume Shou Kubonaga Tomoya Horiuchi Masamichi Hongo Jo Nishida Yuta Okugawa Ayaka Fujiwara Miho Fukuda Shunsuke Hidaka Keita W. Suzuki Masaki Miya Hitoshi Araki Hiroki Yamanaka Atsushi Maruyama Kazushi Miyashita Reiji Masuda Toshifumi Minamoto Michio Kondoh 《PloS one》2016,11(3)
Recent studies in streams and ponds have demonstrated that the distribution and biomass of aquatic organisms can be estimated by detection and quantification of environmental DNA (eDNA). In more open systems such as seas, it is not evident whether eDNA can represent the distribution and biomass of aquatic organisms because various environmental factors (e.g., water flow) are expected to affect eDNA distribution and concentration. To test the relationships between the distribution of fish and eDNA, we conducted a grid survey in Maizuru Bay, Sea of Japan, and sampled surface and bottom waters while monitoring biomass of the Japanese jack mackerel (Trachurus japonicus) using echo sounder technology. A linear model showed a high R2 value (0.665) without outlier data points, and the association between estimated eDNA concentrations from the surface water samples and echo intensity was significantly positive, suggesting that the estimated spatial variation in eDNA concentration can reflect the local biomass of the jack mackerel. We also found that a best-fit model included echo intensity obtained within 10–150 m from water sampling sites, indicating that the estimated eDNA concentration most likely reflects fish biomass within 150 m in the bay. Although eDNA from a wholesale fish market partially affected eDNA concentration, we conclude that eDNA generally provides a ‘snapshot’ of fish distribution and biomass in a large area. Further studies in which dynamics of eDNA under field conditions (e.g., patterns of release, degradation, and diffusion of eDNA) are taken into account will provide a better estimate of fish distribution and biomass based on eDNA. 相似文献
109.
Masamichi Yamashita Yoshihiko Hirohashi Toshihiko Torigoe Hiroki Kusumoto Aiko Murai Tomohiro Imagawa Noriyuki Sato 《PloS one》2016,11(1)
Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined by their abilities of tumor initiation, self-renewal and differentiation. In a previous study, we showed by gene knockdown using siRNA and gene overexpression experiments that Dnaj (Hsp40) homolog, subfamily B, member 8 (DNAJB8), a role in the maintenance, of renal cell carcinoma CSCs/CICs. In the present study, we established Dnajb8 knockout (KO) renal cell carcinoma (RCC) line cells (RenCa cells) and analyzed the cells to confirm the function of Dnajb8 in RCC CSCs/CICs. Dnajb8 KO cells showed reduced ratios of side population cells and reduced sphere forming ability. An in vivo single cell tumor initiation assay revealed that the numbers of CSCs/CICs were 3 in 4 wild-type RenCa cells and 1 in 4 Dnajb8 KO cells. Dnajb8 KO cells showed sensitivity to Docetaxel. On the other hand, Dnajb8 KO cells did not show any sensitivities to stresses including low pH, low glucose, heat shock and sensitivity to cisplatin. The results indicate that Dnajb8 has a role in tumor initiation, side population ratio and sphere formation but it is dispensable for stress responses. 相似文献
110.
Takayuki Kishi Hiroki Kawana Misa Sayama Kumiko Makide Asuka Inoue Yuko Otani Tomohiko Ohwada Junken Aoki 《Biochemistry and Biophysics Reports》2016
Upon various stimulations, mast cells (MCs) release a wide variety of chemical mediators stored in their cytoplasmic granules, which then initiates subsequent allergic reactions. Lysophosphatidylserine (LysoPS), a kind of lysophospholipid, potentiates the histamine release from MCs triggered by antigen stimulation. We previously showed through structure-activity studies of LysoPS analogs that LysoPS with a methyl group at the carbon of the serine residue, i.e., lysophosphatidylthreonine (LysoPT), is extremely potent in stimulating the MC degranulation. In this study, as our continuing study to identify more potent LysoPS analogs, we developed LysoPS analogs with fatty acid surrogates. We found that the substitution of oleic acid to an aromatic fatty acid surrogate (C3-pH-p-O-C11) in 2-deoxy-1-LysoPS resulted in significant increase in the ability to induce MCs degranulation compared with 2-deoxy-1-LysoPS with oleic acid. Conversion of the serine residue into the threonine residue further increased the activity of MC degranulation both in vitro and in vivo. The resulting super agonist, 2-deoxy-LysoPT with C3-pH-p-O-C11, will be a useful tool to elucidate the mechanisms of stimulatory effect of LysoPS on MC degranulation. 相似文献