全文获取类型
收费全文 | 1809篇 |
免费 | 106篇 |
出版年
2021年 | 21篇 |
2019年 | 9篇 |
2018年 | 20篇 |
2017年 | 21篇 |
2016年 | 22篇 |
2015年 | 58篇 |
2014年 | 56篇 |
2013年 | 198篇 |
2012年 | 73篇 |
2011年 | 73篇 |
2010年 | 56篇 |
2009年 | 58篇 |
2008年 | 89篇 |
2007年 | 80篇 |
2006年 | 75篇 |
2005年 | 70篇 |
2004年 | 59篇 |
2003年 | 81篇 |
2002年 | 59篇 |
2001年 | 35篇 |
2000年 | 53篇 |
1999年 | 38篇 |
1998年 | 22篇 |
1997年 | 14篇 |
1996年 | 15篇 |
1995年 | 21篇 |
1994年 | 9篇 |
1993年 | 9篇 |
1992年 | 33篇 |
1991年 | 35篇 |
1990年 | 44篇 |
1989年 | 37篇 |
1988年 | 38篇 |
1987年 | 33篇 |
1986年 | 28篇 |
1985年 | 34篇 |
1984年 | 13篇 |
1983年 | 17篇 |
1982年 | 15篇 |
1979年 | 15篇 |
1978年 | 14篇 |
1977年 | 19篇 |
1976年 | 11篇 |
1975年 | 11篇 |
1974年 | 10篇 |
1973年 | 14篇 |
1972年 | 13篇 |
1971年 | 10篇 |
1970年 | 13篇 |
1967年 | 12篇 |
排序方式: 共有1915条查询结果,搜索用时 31 毫秒
91.
Mayumi Hachinohe Midori Yamane Daiki Akazawa Kazuhiro Ohsawa Mayumi Ohno Yuzu Terashita Hiroshi Masumoto 《PloS one》2013,8(1)
The regulation of energy metabolism, such as calorie restriction (CR), is a major determinant of cellular longevity. Although augmented gluconeogenesis is known to occur in aged yeast cells, the role of enhanced gluconeogenesis in aged cells remains undefined. Here, we show that age-enhanced gluconeogenesis is suppressed by the deletion of the tdh2 gene, which encodes glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a protein that is involved in both glycolysis and gluconeogenesis in yeast cells. The deletion of TDH2 restores the chronological lifespan of cells with deletions of both the HST3 and HST4 genes, which encode yeast sirtuins, and represses the activation of gluconeogenesis. Furthermore, the tdh2 gene deletion can extend the replicative lifespan in a CR pathway-dependent manner. These findings demonstrate that the repression of enhanced gluconeogenesis effectively extends the cellular lifespan. 相似文献
92.
Yasushi Toge Yukihide Nishimura Jeffrey R. Basford Takako Nogawa Midori Yamanaka Takeshi Nakamura Munehito Yoshida Akira Nagano Fumihiro Tajima 《PloS one》2013,8(12)
Objective
To assess the separate effects of thumb and finger extension/flexion on median nerve position and cross-sectional area.Methods
Ultrasonography was used to assess median nerve transverse position and cross-sectional area within the carpal tunnel at rest and its movement during volitional flexion of the individual digits of the hand. Both wrists of 165 normal subjects (11 men, 4 women, mean age, 28.6, range, 22 to 38) were studied.Results
Thumb flexion resulted in transverse movement of the median nerve in radial direction (1.2±0.6 mm), whereas flexion of the fingers produced transverse movement in ulnar direction, which was most pronounced during flexion of the index and middle fingers (3.2±0.9 and 3.1±1.0 mm, respectively). Lesser but still statistically significant movements were noted with flexion of the ring finger (2.0±0.8 mm) and little finger (1.2±0.5 mm). Flexion of the thumb or individual fingers did not change median nerve cross-sectional area (8.5±1.1 mm2).Conclusions
Volitional flexion of the thumb and individual fingers, particularly the index and middle fingers, produced significant transverse movement of the median nerve within the carpal tunnel but did not alter the cross-sectional area of the nerve. The importance of these findings on the understanding of the pathogenesis of the carpal tunnel syndrome and its treatment remains to be investigated. 相似文献93.
Youki Ueda Midori Takeda Kyoko Mori Hiromichi Dansako Takaji Wakita Hye-Sook Kim Akira Sato Yusuke Wataya Masanori Ikeda Nobuyuki Kato 《PloS one》2013,8(8)
Background
Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a global health problem. Although new triple therapy (pegylated-interferon, ribavirin, and telaprevir/boceprevir) has recently been started and is expected to achieve a sustained virologic response of more than 70% in HCV genotype 1 patients, there are several problems to be resolved, including skin rash/ageusia and advanced anemia. Thus a new type of anti-HCV drug is still needed.Methodology/Principal Findings
Recently developed HCV drug assay systems using HCV-RNA-replicating cells (e.g., HuH-7-derived OR6 and Li23-derived ORL8) were used to evaluate the anti-HCV activity of drug candidates. During the course of the evaluation of anti-HCV candidates, we unexpectedly found that two preclinical antimalarial drugs (N-89 and its derivative N-251) showed potent anti-HCV activities at tens of nanomolar concentrations irrespective of the cell lines and HCV strains of genotype 1b. We confirmed that replication of authentic HCV-RNA was inhibited by these drugs. Interestingly, however, this anti-HCV activity did not work for JFH-1 strain of genotype 2a. We demonstrated that HCV-RNA-replicating cells were cured by treatment with only N-89. A comparative time course assay using N-89 and interferon-α demonstrated that N-89-treated ORL8 cells had more rapid anti-HCV kinetics than did interferon-α-treated cells. This anti-HCV activity was largely canceled by vitamin E. In combination with interferon-α and/or ribavirin, N-89 or N-251 exhibited a synergistic inhibitory effect.Conclusions/Significance
We found that the preclinical antimalarial drugs N-89 and N-251 exhibited very fast and potent anti-HCV activities using cell-based HCV-RNA-replication assay systems. N-89 and N-251 may be useful as a new type of anti-HCV reagents when used singly or in combination with interferon and/or ribavirin. 相似文献94.
95.
Tadanobu Takahashi Sawako Kawagishi Midori Masuda Takashi Suzuki 《Glycoconjugate journal》2013,30(7):709-716
Association of a sulfated galactosyl ceramide, sulfatide, with the viral envelope glycoprotein hemagglutinin (HA) delivered to the cell surface is required for influenza A virus (IAV) replication through efficient translocation of the newly synthesized viral nucleoprotein from the nucleus to the cytoplasm. To determine whether the ectodomain of HA can bind to sulfatide, a secreted-type HA (sHA), in which the transmembrane region and cytoplasmic tail were deleted, was generated by using a baculovirus expression system. The receptor binding ability and antigenic structure of sHA were evaluated by a hemagglutination assay, solid-phase binding assay and hemagglutination inhibition assay. sHA showed subtype-specific antigenicity and binding ability to both sulfatide and gangliosides. Kinetics of sHA binding to sulfatide and GD1a was demonstrated by quartz crystal microbalance (QCM) analysis. QCM analysis showed that the sHA bound with the association rate constant (k on) of 1.41?×?104 M?1 sec?1, dissociation rate constant (k off) of 2.03?×?10?4 sec?1 and K d of 1.44?×?10?8 M to sulfatide immobilized on a sensor chip. The k off values of sHA were similar for sulfatide and GD1a, whereas the k on value of sHA binding to sulfatide was 2.56-times lower than that of sHA binding to GD1a. The results indicate that sulfatide directly binds to the ectodomain of HA with high affinity. 相似文献
96.
Yuriko Furuya Atsushi Inagaki Masud Khan Kaoru Mori Josef M. Penninger Midori Nakamura Nobuyuki Udagawa Kazuhiro Aoki Keiichi Ohya Kohji Uchida Hisataka Yasuda 《The Journal of biological chemistry》2013,288(8):5562-5571
To date, parathyroid hormone is the only clinically available bone anabolic drug. The major difficulty in the development of such drugs is the lack of clarification of the mechanisms regulating osteoblast differentiation and bone formation. Here, we report a peptide (W9) known to abrogate osteoclast differentiation in vivo via blocking receptor activator of nuclear factor-κB ligand (RANKL)-RANK signaling that we surprisingly found exhibits a bone anabolic effect in vivo. Subcutaneous administration of W9 three times/day for 5 days significantly augmented bone mineral density in mouse cortical bone. Histomorphometric analysis showed a decrease in osteoclastogenesis in the distal femoral metaphysis and a significant increase in bone formation in the femoral diaphysis. Our findings suggest that W9 exerts bone anabolic activity. To clarify the mechanisms involved in this activity, we investigated the effects of W9 on osteoblast differentiation/mineralization in MC3T3-E1 (E1) cells. W9 markedly increased alkaline phosphatase (a marker enzyme of osteoblasts) activity and mineralization as shown by alizarin red staining. Gene expression of several osteogenesis-related factors was increased in W9-treated E1 cells. Addition of W9 activated p38 MAPK and Smad1/5/8 in E1 cells, and W9 showed osteogenesis stimulatory activity synergistically with BMP-2 in vitro and ectopic bone formation. Knockdown of RANKL expression in E1 cells reduced the effect of W9. Furthermore, W9 showed a weak effect on RANKL-deficient osteoblasts in alkaline phosphatase assay. Taken together, our findings suggest that this peptide may be useful for the treatment of bone diseases, and W9 achieves its bone anabolic activity through RANKL on osteoblasts accompanied by production of several autocrine factors. 相似文献
97.
Kazuyuki Nakamura Hirofumi Kodera Tenpei Akita Masaaki Shiina Mitsuhiro Kato Hideki Hoshino Hiroshi Terashima Hitoshi Osaka Shinichi Nakamura Jun Tohyama Tatsuro Kumada Tomonori Furukawa Satomi Iwata Takashi Shiihara Masaya Kubota Satoko Miyatake Eriko Koshimizu Kiyomi Nishiyama Mitsuko Nakashima Yoshinori Tsurusaki Noriko Miyake Kiyoshi Hayasaka Kazuhiro Ogata Atsuo Fukuda Naomichi Matsumoto Hirotomo Saitsu 《American journal of human genetics》2013
98.
Yoshikazu Izumi Kuninori Sato Yoshiki Tani Koichi Ogata 《Bioscience, biotechnology, and biochemistry》2013,77(11):2683-2684
Vitamin B6 is synthesized by green Cytisus scoparius callus and green Phellodendron amurense callus cultured on Linsmaier and Skoog Agar-medium with 10?5m of ±-naphthaleneacetic acid (NAA) and 10?6 m of 6-benzyladenine (BA). Even when thiamine and inositol were omitted from this medium, the growth and vitamin B6 content of Cytisus scoparius callus did not change. Vitamin B6 contents of clones of the calluses varied and were unstable during long-term subculture. Clonal selection was repeated to obtain stable strains with high vitamin B6 content, and the vitamin B6 content of one strain of green Cytisus scoparius callus became 4-times higher than that of the green leaves. 相似文献
99.
Takuo Sakai Tatsurokuro Tochikura Koichi Ogata 《Bioscience, biotechnology, and biochemistry》2013,77(8):737-741
In this study, the authors developed a simplified method for the separation and the quantitative determination of nucleosides and bases, using paper electraophoretic technique. By this method, nucleosides and bases were well separated and determined in a fairly short time. Thus, this method was expected to be as accurate as the published methods and was believed to be a better method for both quantitative determination and detection of the nucleosides and bases in a large number of samples. 相似文献
100.