全文获取类型
收费全文 | 3717篇 |
免费 | 163篇 |
国内免费 | 3篇 |
出版年
2022年 | 14篇 |
2021年 | 33篇 |
2020年 | 14篇 |
2019年 | 20篇 |
2018年 | 30篇 |
2017年 | 25篇 |
2016年 | 42篇 |
2015年 | 66篇 |
2014年 | 86篇 |
2013年 | 325篇 |
2012年 | 188篇 |
2011年 | 171篇 |
2010年 | 110篇 |
2009年 | 106篇 |
2008年 | 188篇 |
2007年 | 205篇 |
2006年 | 210篇 |
2005年 | 217篇 |
2004年 | 225篇 |
2003年 | 246篇 |
2002年 | 233篇 |
2001年 | 71篇 |
2000年 | 42篇 |
1999年 | 56篇 |
1998年 | 57篇 |
1997年 | 53篇 |
1996年 | 40篇 |
1995年 | 40篇 |
1994年 | 42篇 |
1993年 | 28篇 |
1992年 | 61篇 |
1991年 | 43篇 |
1990年 | 38篇 |
1989年 | 28篇 |
1988年 | 49篇 |
1987年 | 34篇 |
1986年 | 27篇 |
1985年 | 33篇 |
1984年 | 39篇 |
1983年 | 36篇 |
1982年 | 47篇 |
1981年 | 37篇 |
1980年 | 30篇 |
1979年 | 20篇 |
1978年 | 20篇 |
1977年 | 22篇 |
1976年 | 20篇 |
1975年 | 20篇 |
1974年 | 17篇 |
1973年 | 12篇 |
排序方式: 共有3883条查询结果,搜索用时 15 毫秒
891.
Jie Liu Jun Shiono Kuniyoshi Shimizu Akiko Kukita Toshio Kukita Ryuichiro Kondo 《Bioorganic & medicinal chemistry letters》2009,19(8):2154-2157
Prostate cancer is the most common cancer in men in Western countries, with a high incidence of bone metastasis. Ganoderic acid DM, with 5α-reductase inhibitory and androgen receptor (AR) binding activity, isolated from the ethanol extracts of Ganoderma lucidum, can inhibit prostate cancer cell growth and block osteoclastogenesis. 相似文献
892.
Wakako Yamada Kenji Nagao Ayako Fujikura Yoshimasa Inagaki Kazuma Tomizuka Toshio Suda Keiyo Takubo 《Biochemical and biophysical research communications》2009,381(3):453-458
In vertebrates, craniofacial formation is accomplished by synergistic interaction of many small elements which are generated independently from distinct germ layers. Because of its complexity, the imbalance of one signaling cascade such as Wnt/β-catenin pathway easily leads to craniofacial malformation, which is the most frequent birth defect in humans. To investigate the developmental role of a newly identified activator of Wnt/β-catenin signaling, Rspo2, we generated and characterized Rspo2−/− mice. We found CLP with mild facial skeletal defects in Rspo2−/− mice. Additionally, Rspo2−/− mice also exhibited distal limb loss and lung hypoplasia, and died immediately after birth with respiratory failure. We showed the apparent reduction of Wnt/β-catenin signaling activity at the branchial arch and the apical ectodermal ridge in Rspo2−/− mice. These findings indicate that Rspo2 regulates midfacial, limb, and lung morphogenesis during development through the Wnt/β-catenin signaling. 相似文献
893.
Two-dimensional electron spin-echo envelope modulation (ESEEM) analysis of the uniformly 15N-labeled archaeal Rieske-type [2Fe-2S] ferredoxin (ARF) from Sulfolobus solfataricus P1 has been conducted in comparison with the previously characterized high-potential protein homologs. Major differences among these proteins were found in the hyperfine sublevel correlation (HYSCORE) lineshapes and intensities of the signals in the (++) quadrant, which are contributed from weakly coupled (non-coordinated) peptide nitrogens near the reduced clusters. They are less pronounced in the HYSCORE spectra of ARF than those of the high-potential protein homologs, and may account for the tuning of Rieske-type clusters in various redox systems. 相似文献
894.
895.
Naoki Watanabe Kentaro Hiramatsu Rieko Miyamoto Kaoru Yasuda Naoko Oshima Dai Shiba Toshio Mochizuki Shoichi Maruyama Yuko Wakamatsu Hisashi Hashimoto 《FEBS letters》2009,583(12):2108-2113
Glis3 is a member of the Gli-similar subfamily. GLIS3 mutations in humans lead to neonatal diabetes, hypothyroidism, and cystic kidney disease. We generated Glis3-deficient mice by gene-targeting. The Glis3−/− mice had significant increases in the basal blood sugar level during the first few days after birth. The high levels of blood sugar are attributed to a decrease in the Insulin mRNA level in the pancreas that is caused by impaired islet development and the subsequent impairment of Insulin-producing cell formation. The pancreatic phenotypes indicate that the Glis3-deficient mice are a model for GLIS3 mutation and diabetes mellitus in humans. 相似文献
896.
897.
Thaís Leal-Silva Flaviane Vieira-Santos Fabrício Marcus Silva Oliveira Luiza de Lima Silva Padro Lucas Kraemer Pablo Hemanoel da Paixo Matias Camila de Almeida Lopes Ana Cristina Loiola Ruas Isabella Carvalho de Azevedo Denise Silva Nogueira Milene Alvarenga Rachid Marcelo Vidigal Caliari Remo Castro Russo Ricardo Toshio Fujiwara Lilian Lacerda Bueno 《PLoS neglected tropical diseases》2021,15(7)
Toxocariasis is a neglected disease that affects people around the world. Humans become infected by accidental ingestion of eggs containing Toxocara canis infective larvae, which upon reaching the intestine, hatch, penetrate the mucosa and migrate to various tissues such as liver, lungs and brain. Studies have indicated that Th2 response is the main immune defense mechanism against toxocariasis, however, there are still few studies related to this response, mainly the IL-33/ST2 pathway. Some studies have reported an increase in IL-33 during helminth infections, including T. canis. By binding to its ST2 receptor, IL-33 stimulating the Th2 polarized immune cell and cytokine responses. Thus, we aimed to investigate the role of the IL-33/ST2 pathway in the context of T. canis larval migration and the immunological and pathophysiological aspects of the infection in the liver, lungs and brain from Wild-Type (WT) BALB/c background and genetically deficient mice for the ST2 receptor (ST2-/-). The most important findings revealed that the IL-33/ST2 pathway is involved in eosinophilia, hepatic and cerebral parasitic burden, and induces the formation of granulomas related to tissue damage and pulmonary dysfunction. However, ST2-/- mice, the immune response was skewed to Th1/Th17 type than Th2, that enhanced the control of parasite burden related to IgG2a levels, tissue macrophages infiltration and reduced lung dysfunction. Collectively, our results demonstrate that the Th2 immune response triggered by IL-33/ST2 pathway mediates susceptibility to T. canis, related to parasitic burden, eosinophilia and granuloma formation in which consequently contributes to tissue inflammation and injury. 相似文献
898.
The ribosomal stalk protein L12 is essential for events dependent on the GTP-binding translation factors. It has been recently shown that ribosomes from Thermus thermophilus contain a heptameric complex L10.(L12)2.(L12)2.(L12)2, rather than the conventional pentameric complex L10.(L12)2.(L12)2. Here we describe the reconstitution of the heptameric complex from purified L10 and L12 and the characterization of its role in elongation factor G-dependent GTPase activity using a hybrid system with Escherichia coli ribosomes. The T. thermophilus heptameric complex resulted in a 2.5-fold higher activity than the E. coli pentameric complex. The structural element of the T. thermophilus complex responsible for the higher activity was investigated using a chimeric L10 protein (Ec-Tt-L10), in which the C-terminal L12-binding site in E. coli L10 was replaced with the same region from T. thermophilus, and two chimeric L12 proteins: Ec-Tt-L12, in which the E. coli N-terminal domain was fused with the T. thermophilus C-terminal domain, and Tt.Ec-L12, in which the T. thermophilus N-terminal domain was fused with the E. coli C-terminal domain. High GTPase turnover was observed with the pentameric chimeric complex formed from E. coli L10 and Ec-Tt-L12 but not with the heptameric complex formed from Ec-Tt-L10 and Tt.Ec-L12. This suggested that the C-terminal region of T. thermophilus L12, rather than the heptameric nature of the complex, was responsible for the high GTPase turnover. Further analyses with other chimeric L12 proteins identified helix alpha6 as the region most likely to contain the responsible element. 相似文献
899.
900.
Kenji Komatsu Yuri Nishikawa Tomohito Ohtsuka Teruaki Taji Ralph S. Quatrano Shigeo Tanaka Yoichi Sakata 《Plant molecular biology》2009,70(3):327-340
We employed a comparative genomic approach to understand protein phosphatase 2C (PP2C)-mediated abscisic acid (ABA) signaling
in the moss Physcomitrella patens. Ectopic expression of Arabidopsis (Arabidopsis thaliana) abi1-1, a dominant mutant allele of ABI1 encoding a PP2C involved in the negative regulation of ABA signaling, caused ABA insensitivity of P. patens both in gene expression of late embryogenesis abundant (LEA) genes and in ABA-induced protonemal growth inhibition. The transgenic
abi1-1 plants showed decreased ABA-induced freezing tolerance, and decreased tolerance to osmotic stress. Analyses of the P. patens genome revealed that only two (PpABI1A and PpABI1B) PP2C genes were related to ABI1. In the ppabi1a null mutants, ABA-induced expression of LEA genes was elevated, and protonemal growth was inhibited with lower ABA concentration compared to the wild type. Moreover,
ABA-induced freezing tolerance of the ppabi1a mutants was markedly enhanced. We provide the genetic evidence that PP2C-mediated ABA signaling is evolutionarily conserved
between Arabidopsis and P. patens.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Accession Numbers: PpABI1A-AB369256, PpABI1B-AB369255, pphn39k21-AB369257. 相似文献