全文获取类型
收费全文 | 1901篇 |
免费 | 193篇 |
国内免费 | 3篇 |
出版年
2022年 | 13篇 |
2021年 | 30篇 |
2020年 | 9篇 |
2019年 | 13篇 |
2018年 | 29篇 |
2017年 | 24篇 |
2016年 | 32篇 |
2015年 | 59篇 |
2014年 | 77篇 |
2013年 | 98篇 |
2012年 | 113篇 |
2011年 | 98篇 |
2010年 | 65篇 |
2009年 | 61篇 |
2008年 | 112篇 |
2007年 | 113篇 |
2006年 | 122篇 |
2005年 | 107篇 |
2004年 | 124篇 |
2003年 | 110篇 |
2002年 | 92篇 |
2001年 | 70篇 |
2000年 | 61篇 |
1999年 | 48篇 |
1998年 | 27篇 |
1997年 | 16篇 |
1996年 | 18篇 |
1995年 | 25篇 |
1994年 | 27篇 |
1993年 | 14篇 |
1992年 | 36篇 |
1991年 | 26篇 |
1990年 | 29篇 |
1989年 | 24篇 |
1988年 | 18篇 |
1987年 | 15篇 |
1986年 | 9篇 |
1985年 | 11篇 |
1984年 | 13篇 |
1983年 | 6篇 |
1982年 | 10篇 |
1981年 | 10篇 |
1980年 | 8篇 |
1979年 | 15篇 |
1978年 | 11篇 |
1977年 | 13篇 |
1975年 | 4篇 |
1974年 | 4篇 |
1971年 | 5篇 |
1966年 | 3篇 |
排序方式: 共有2097条查询结果,搜索用时 281 毫秒
991.
992.
Tsuyoshi HOSOYA Yukiko SAITO Yukio HARADA Kazuaki TANAKA Yan-Jie ZHAO Makoto KAKISHIMA 《菌物学报》2013,32(3):448-456
对日本新记录种Stamnaria americana进行了描述和图示。尽管低温适宜该种子囊孢子的萌发,它在20℃生长最好。DNA序列分析的结果表明,其分类地位应该从柔膜菌科转入锤舌菌科。 相似文献
993.
A large number of nucleotide sequences of various pathogens are available in public databases. The growth of the datasets has resulted in an enormous increase in computational costs. Moreover, due to differences in surveillance activities, the number of sequences found in databases varies from one country to another and from year to year. Therefore, it is important to study resampling methods to reduce the sampling bias. A novel algorithm–called the closest-neighbor trimming method–that resamples a given number of sequences from a large nucleotide sequence dataset was proposed. The performance of the proposed algorithm was compared with other algorithms by using the nucleotide sequences of human H3N2 influenza viruses. We compared the closest-neighbor trimming method with the naive hierarchical clustering algorithm and -medoids clustering algorithm. Genetic information accumulated in public databases contains sampling bias. The closest-neighbor trimming method can thin out densely sampled sequences from a given dataset. Since nucleotide sequences are among the most widely used materials for life sciences, we anticipate that our algorithm to various datasets will result in reducing sampling bias. 相似文献
994.
Yu-Yan Lan Tzu-Hao Yeh Wei-Hung Lin Shih-Yi Wu Hsiao-Ching Lai Fang-Hsin Chang Kenzo Takada Yao Chang 《PloS one》2013,8(2)
Zta is a lytic transactivator of Epstein-Barr virus (EBV) and has been shown to promote migration and invasion of epithelial cells. Although previous studies indicate that Zta induces expression of matrix metalloproteinase (MMP) 9 and MMP1, direct evidence linking the MMPs to Zta-induced cell migration and invasion is still lacking. Here we performed a series of in vitro studies to re-examine the expression profile and biologic functions of Zta-induced MMPs in epithelial cells derived from nasopharyngeal carcinoma. We found that, in addition to MMP9, MMP3 was a new target gene upregulated by Zta. Ectopic Zta expression in EBV-negative cells increased both mRNA and protein production of MMP3. Endogenous Zta also contributed to induction of MMP3 expression, migration and invasion of EBV-infected cells. Zta activated the MMP3 promoter through three AP-1 elements, and its DNA-binding domain was required for the promoter binding and MMP3 induction. We further tested the effects of MMP3 and MMP9 on cell motility and invasiveness in vitro. Zta-promoted cell migration required MMP3 but not MMP9. On the other hand, both MMP3 and MMP9 were essential for Zta-induced cell invasion, and co-expression of the two MMPs synergistically increased cell invasiveness. Therefore, this study provides integrated evidence demonstrating that, at least in the in vitro cell models, Zta drives cell migration and invasion through MMPs. 相似文献
995.
Motoi Hashiba Masafumi Ono Hideyuki Hyogo Yukio Ikeda Kosei Masuda Reiko Yoshioka Yoichi Ishikawa Yuri Nagata Kensuke Munekage Tsunehiro Ochi Akira Hirose Yasuko Nozaki-Fujimura Shuhei Noguchi Nobuto Okamoto Kazuaki Chayama Narufumi Suganuma Toshiji Saibara 《PloS one》2013,8(11)
Patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) often have metabolic disorders including insulin resistance and type 2 diabetes mellitus (T2DM). We clarified the predictive factors in glucose metabolism for progression of hepatic fibrosis in patients with NAFLD by the 75-g oral glucose tolerance test (75gOGTT) and a continuous glucose monitoring system (CGMS). One hundred sixty-nine patients (68 female and 101 male patients) with biopsy-proven NAFLD with performance with 75gOGTT were enrolled and divided into four groups according to the stage of hepatic fibrosis (F0–3). The proportion of patients with T2DM significantly gradually increased, HbA1c and the homeostasis model assessment of insulin resistance were significantly elevated, and 1,5-anhydroglucitol (1,5-AG) was remarkably decreased with the progression of fibrosis. In the 75gOGTT, both plasma glucose and insulin secretion were remarkably increased with the progression of fibrosis. The only factor significantly associated with advanced fibrosis was 1,5-AG (P = 0.008) as determined by multivariate logistic regression analysis. We next evaluated the changes in blood glucose during 24 hours by monitoring with the CGMS to confirm the relationship between glycemic variability and progression of fibrosis. Variability of median glucose, standard deviation of median glucose (P = 0.0022), maximum blood glucose (P = 0.0019), and ΔMin–max blood glucose (P = 0.0029) were remarkably higher in severe fibrosis than in mild fibrosis.
Conclusion
Hyperinsulinemia and hyperglycemia, especially glycemic variability, are important predictive factors in glucose impairment for the progression of hepatic fibrosis in NAFLD. 相似文献996.
Masaaki Fujita Katsuaki Ieguchi Dora M. Cedano-Prieto Andrew Fong Charles Wilkerson Jane Q. Chen Mac Wu Su-Hao Lo Anthony T. W. Cheung Machelle D. Wilson Robert D. Cardiff Alexander D. Borowsky Yoko K. Takada Yoshikazu Takada 《The Journal of biological chemistry》2013,288(27):19593-19603
Insulin-like growth factor-1 (IGF1) is a major therapeutic target for cancer. We recently reported that IGF1 directly binds to integrins (αvβ3 and α6β4) and induces ternary complex formation (integrin-IGF1-IGF1 receptor (IGF1R)) and that the integrin binding-defective mutant of IGF1 (R36E/R37E) is defective in signaling and ternary complex formation. These findings predict that R36E/R37E competes with WT IGF1 for binding to IGF1R and inhibits IGF signaling. Here, we described that excess R36E/R37E suppressed cell viability increased by WT IGF1 in vitro in non-transformed cells. We studied the effect of R36E/R37E on viability and tumorigenesis in cancer cell lines. We did not detect an effect of WT IGF1 or R36E/R37E in cancer cells under anchorage-dependent conditions. However, under anchorage-independent conditions, WT IGF1 enhanced cell viability and induced signals, whereas R36E/R37E did not. Notably, excess R36E/R37E suppressed cell viability and signaling induced by WT IGF1 under anchorage-independent conditions. Using cancer cells stably expressing WT IGF1 or R36E/R37E, we determined that R36E/R37E suppressed tumorigenesis in vivo, whereas WT IGF1 markedly enhanced it. R36E/R37E suppressed the binding of WT IGF1 to the cell surface and the subsequent ternary complex formation induced by WT IGF1. R36E/R37E suppressed activation of IGF1R by insulin. WT IGF1, but not R36E/R37E, induced ternary complex formation with the IGF1R/insulin receptor hybrid. These findings suggest that 1) IGF1 induces signals under anchorage-independent conditions and that 2) R36E/R37E acts as a dominant-negative inhibitor of IGF1R (IGF1 decoy). Our results are consistent with a model in which ternary complex formation is critical for IGF signaling. 相似文献
997.
Osamu Noyori Eri Nakayama Junki Maruyama Reiko Yoshida Ayato Takada 《Biochemical and biophysical research communications》2013
Apoptotic death of virus-infected cells is generally thought to be a defense mechanism to limit the spread of infectious virions by eliminating virus-producing cells in host animals. On the other hand, several viruses have been shown to have anti-apoptotic mechanisms to facilitate efficient viral replication and transmission. In this study, we found that the filovirus glycoprotein (GP) expressed on cell surfaces formed a steric shield over the Fas molecule and that GP-expressing cells showed resistance to cell death induced by a Fas agonistic antibody. These results suggest that filovirus GP-mediated steric shielding may interfere with the Fas-induced apoptotic signal transduction in infected cells and serve as an immune evasion mechanism for filoviruses. 相似文献
998.
999.
Mei Kikumoto Shohei Nogami Tadayoshi Kanao Jun Takada Kazuo Kamimura 《Applied and environmental microbiology》2013,79(1):113-120
Thiosulfate dehydrogenase is known to play a significant role in thiosulfate oxidation in the acidophilic, obligately chemolithoautotroph, Acidithiobacillus ferrooxidans. Enzyme activity measured using ferricyanide as the electron acceptor was detected in cell extracts of A. ferrooxidans ATCC 23270 grown on tetrathionate or sulfur, but no activity was detected in ferrous iron-grown cells. The enzyme was enriched 63-fold from cell extracts of tetrathionate-grown cells. Maximum enzyme activity (13.8 U mg−1) was observed at pH 2.5 and 70°C. The end product of the enzyme reaction was tetrathionate. The enzyme reduced neither ubiquinone nor horse heart cytochrome c, which serves as an electron acceptor. A major protein with a molecular mass of ∼25 kDa was detected in the partially purified preparation. Heme was not detected in the preparation, according to the results of spectroscopic analysis and heme staining. The open reading frame of AFE_0042 was identified by BLAST by using the N-terminal amino acid sequence of the protein. The gene was found within a region that was previously noted for sulfur metabolism-related gene clustering. The recombinant protein produced in Escherichia coli had a molecular mass of ∼25 kDa and showed thiosulfate dehydrogenase activity, with maximum enzyme activity (6.5 U mg−1) observed at pH 2.5 and 50°C. 相似文献
1000.
Yoshitake Takada Hiroko Sasama Takashi Sayama Akio Kikuchi Shin Kato Masao Ishimoto Chigen Tsukamoto 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2013,126(3):721-731
Although certain saponins in soybean seeds have been reported to have health benefits, group A acetyl saponins cause undesirable bitter and astringent tastes in soy products. Therefore, reduction or elimination of group A saponins is an important target for soybean breeders. A wide survey of cultivated and wild soybean germplasm identified a mutant line that lacked group A saponins. The absence of soyasapogenol A, a group A saponin aglycone, is controlled by a single recessive allele, sg-5 that mapped genetically near the SSR marker, Satt117, on soybean chromosome 15 (linkage group E). The locus is epistatic to Sg-1, which controls the terminal sugar variation on the C-22 sugar chain of soyasapogenol A, and allelic differences at this locus lead to changes in the amount of DDMP saponins and their derivatives group B and E products. These findings provide a new insight into the biosynthetic pathway of soybean saponins, and identify a genetic approach that can be applied to improve the quality of foods produced from soybean. 相似文献