全文获取类型
收费全文 | 5264篇 |
免费 | 369篇 |
国内免费 | 393篇 |
出版年
2024年 | 5篇 |
2023年 | 73篇 |
2022年 | 188篇 |
2021年 | 266篇 |
2020年 | 183篇 |
2019年 | 221篇 |
2018年 | 217篇 |
2017年 | 166篇 |
2016年 | 224篇 |
2015年 | 303篇 |
2014年 | 389篇 |
2013年 | 417篇 |
2012年 | 467篇 |
2011年 | 399篇 |
2010年 | 253篇 |
2009年 | 233篇 |
2008年 | 261篇 |
2007年 | 190篇 |
2006年 | 183篇 |
2005年 | 194篇 |
2004年 | 167篇 |
2003年 | 160篇 |
2002年 | 116篇 |
2001年 | 121篇 |
2000年 | 89篇 |
1999年 | 107篇 |
1998年 | 53篇 |
1997年 | 37篇 |
1996年 | 42篇 |
1995年 | 40篇 |
1994年 | 34篇 |
1993年 | 22篇 |
1992年 | 30篇 |
1991年 | 24篇 |
1990年 | 31篇 |
1989年 | 8篇 |
1988年 | 17篇 |
1987年 | 12篇 |
1986年 | 9篇 |
1985年 | 8篇 |
1984年 | 10篇 |
1983年 | 8篇 |
1982年 | 7篇 |
1981年 | 5篇 |
1980年 | 6篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1975年 | 6篇 |
1974年 | 3篇 |
排序方式: 共有6026条查询结果,搜索用时 31 毫秒
111.
Colleen M. McMichael Gregory D. Reynolds Lisa M. Koch Chao Wang Nan Jiang Jeanette Nadeau Fred D. Sack Max B. Gelderman Jianwei Pan Sebastian Y. Bednarek 《The Plant cell》2013,25(10):3910-3925
STOMATAL CYTOKINESIS DEFECTIVE1 (SCD1) encodes a putative Rab guanine nucleotide exchange factor that functions in membrane trafficking and is required for cytokinesis and cell expansion in Arabidopsis thaliana. Here, we show that the loss of SCD2 function disrupts cytokinesis and cell expansion and impairs fertility, phenotypes similar to those observed for scd1 mutants. Genetic and biochemical analyses showed that SCD1 function is dependent upon SCD2 and that together these proteins are required for plasma membrane internalization. Further specifying the role of these proteins in membrane trafficking, SCD1 and SCD2 proteins were found to be associated with isolated clathrin-coated vesicles and to colocalize with clathrin light chain at putative sites of endocytosis at the plasma membrane. Together, these data suggest that SCD1 and SCD2 function in clathrin-mediated membrane transport, including plasma membrane endocytosis, required for cytokinesis and cell expansion. 相似文献
112.
Xingfeng Zheng Xingfeng Zheng Yanfei Mao Jianmei Cai Yonghua Li Wenwu Liu 《Free radical research》2013,47(5):478-484
Hydrogen gas was reported to reduce reactive oxygen species and alleviate cerebral, myocardial and hepatic ischemia/reperfusion (I/R) injuries. This paper studied the effect of hydrogen-rich saline, which was easier for clinical application, on the intestinal I/R injury. Model of intestinal I/R injury was induced in male Sprague-Dawley rats. Physiological saline, hydrogen-rich saline or nitrogen-rich saline (5 ml/kg) was administered via intravenous infusion at 10 min before reperfusion, respectively. The intestine damage was detected microscopically and was assessed by Chiu score system after I/R injury. In addition, serum DAO activity, TNF-α, IL-1β and IL-6 levels, tissue MDA, protein carbonyl and MPO activity were all increased significantly by I/R injury. Hydrogen-rich saline reduced these markers and relieved morphological intestinal injury, while no significant reduction was observed in the nitrogen-rich saline-treated animals. In conclusion, hydrogen-rich saline protected the small intestine against I/R injury, possibly by reduction of inflammation and oxidative stress. 相似文献
113.
114.
Lorene Rozier Yige Guo Shaun Peterson Mai Sato Richard Baer Jean Gautier Yinghui Mao 《Molecular cell》2013,49(6):1097-1107
- Download : Download high-res image (178KB)
- Download : Download full-size image
115.
You-An Mao Ke-Jun Zhong Wan-Zhi Wei Xin-Liang Wei Hong-Bing Lu 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):89-94
The effect of N′-nitrosonornicotine (NNN), one of the tobacco-specific nitrosamines, on the catalytic activity of glutamate dehydrogenase (GLDH) in the α-ketoglutarate amination, using reduced nicotinamide adenine dinucleotide as coenzyme, was studied by a chronoamperometric method. The maximum reaction rate of the enzyme-catalyzed reaction and the Michaelis-Menten constant, or the apparent Michaelis-Menten constant, were determined in the absence and presence of NNN. NNN remarkably inhibited the bio-catalysis activity of GLDH, and was a reversible competitive inhibitior with Ki, estimated as 199?μmol?l?1 at 25°C and pH 8.0. 相似文献
116.
Xia Qin Zhen-Quan Sun Xue-Wei Zhang Xiao-Jing Dai Shan-Shan Mao Yong-Mei Zhang 《Journal of physiology and biochemistry》2013,69(4):707-718
Propofol exhibits neuroprotective effects against hypoxic–ischemic brain injury, but the underlying mechanisms are still not clear. Toll-like receptor 4 (TLR4) plays a considerable role in the induction of innate immune and inflammatory responses. The purposes of this study are to investigate the effect of propofol on the oxygen and glucose deprivation (OGD)/reoxygenation (OGD/R) BV2 microglia and to explore the role of TLR4/myeloid differentiation protein 88 (MyD88)/nuclear factor-kappa B (NF-κB) pathway in the neuroprotective effects of propofol. BV2 microglia were placed into an airtight chamber and in glucose-free medium for OGD/reoxygenation. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay. TLR4 and its downstream signaling molecules, MyD88 and NF-κB expressions were detected by Western blotting. Level of tumor necrosis factor alpha (TNF-α) in culture medium was determined with enzyme-linked immunosorbent assay. BV2 microglia apoptosis was determined by flow cytometry. We found that pretreatment with propofol significantly alleviated the hypoxic injury in BV2 microglia. Propofol inhibited upregulation of TLR4, MyD88, and NF-κB expressions in BV2 microglia exposed to OGD/reoxygenation. Propofol pretreatment also significantly reduced the production of TNF-α and apoptosis in OGD/reoxygenation BV2 microglia. The results indicated that TLR4 and its downstream MyD88-dependent signaling pathway contributed to neuroprotection of propofol to microglia exposed to OGD/reoxygenation. 相似文献
117.
Longfei Mao Wynand S. Verwoerd 《Journal of industrial microbiology & biotechnology》2013,40(10):1161-1180
Synechocystis sp. PCC 6803 has been considered as a promising biocatalyst for electricity generation in recent microbial fuel cell research. However, the innate maximum current production potential and underlying metabolic pathways supporting the high current output are still unknown. This is mainly due to the fact that the high-current production cell phenotype results from the interaction among hundreds of reactions in the metabolism and it is impossible for reductionist methods to characterize the pathway selection in such a metabolic state. In this study, we employed computational metabolic techniques, flux balance analysis, and flux variability analysis, to exploit the maximum current outputs of Synechocystis sp. PCC 6803, in five electron transfer cases, namely, ferredoxin- and plastoquinol-dependent electron transfers under photoautotrophic cultivation, and NADH-dependent mediated electron transfer under photoautotrophic, heterotrophic, and mixotrophic conditions. In these five modes, the maximum current outputs were computed as 0.198, 0.7918, 0.198, 0.4652, and 0.4424 A gDW?1, respectively. Comparison of the five operational modes suggests that plastoquinol-/c-type cytochrome-targeted electricity generation had an advantage of liberating the highest current output achievable for Synechocystis sp. PCC 6803. On the other hand, the analysis indicates that the currency metabolite, NADH-, dependent electricity generation can rely on a number of reactions from different pathways, and is thus more robust against environmental perturbations. 相似文献
118.
Curcumin is the major constituent of turmeric plant, an ancient spice widely used in Indian cuisine and traditional herbal medicine. Recently, the potential medical use of curcumin as anti‐cancer and anti‐inflammatory agent has set off an upsurge in research into the mechanism for its broad biological effects. We showed that CRM1, an important nuclear exportin, is a cellular target of curcumin by serious experimental and theoretical investigation. Using a nuclear export functional assay, we observed a clear and rapid shift of cargo proteins from a cytoplasmic localization to the nucleus when treated with curcumin or its structural analogue dibenzylideneacetone (DBA). We demonstrated that curcumin could specifically target the conserved Cys528 of CRM1 through mass spectrometric analysis and in vivo experiments. Furthermore, computational modeling has revealed that curcumin could be correctly docked into the hydrophobic pocket of CRM1 judged from shape complementarity and putative molecular interactions. The Michael acceptor moiety on curcumin is within the appropriate distance to enable Michael reaction with Cys residue of CRM1. More importantly, we showed that nuclear retention of FOXO1 could be observed in the presence of Leptomycin B (LMB) or curcumin whereas in cells expressing the CRM1‐Cys528 mutant, only a cytoplasmic localization was observed. The inhibition of nuclear traffic by curcumin may account for its myriad of biological effects, particularly for its therapeutic properties in cancer and inflammatory diseases. Our findings may have important implications for further clinical investigation of curcumin . 相似文献
119.
Nonunion of fractured bones is a common clinical problem for orthopedic surgeons. This study aimed to investigate the effects of simvastatin locally applied from calcium sulfate (CS) combined with a mesenchymal stem cell (MSC) sheet on fracture healing. In vitro, the proliferation and differentiation of rat bone marrow–derived MSCs stimulated by simvastatin were investigated. In vivo, an osteotomy model was made in rat tibia, and fractured tibias were treated with CS, CS/simvastatin, CS/MSC sheet or simvastatin-loaded CS with MSC or untreated (control). Tibias were harvested at 2 or 8 weeks and underwent real-time quantitative polymerase chain reaction, x-ray, micro-CT and histological analysis. The expression levels of bone morphogenetic protein 2, alkaline phosphatase, osteocalcin, osteoprotegerin and vascular endothelial growth factor of simvastatin-induced MSCs increased with the concentrations of the simvastatin, significantly higher than those in the MSCs group. At 2 weeks, the CS/simvastatin/MSC sheet group showed significantly higher expressions of bone morphogenetic protein 2, alkaline phosphatase, osteocalcin, osteoprotegerin and vascular endothelial growth factor, with more callus formation around the fracture site compared with the other four groups. At 8 weeks, complete bone union was obtained in the CS/simvastatin/MSC sheet group. By contrast, newly regenerated bone tissue partially bridged the gap in the CS/simvastatin group and the CS/MSC sheet group; the control and CS group showed nonunion of the tibia. These results show that both simvastatin and the MSC sheet contributed to the formation of new bone and that the tibia fracture was completely healed by transplantation of the MSC sheet with locally applied simvastatin. Such MSC sheet with locally applied simvastatin might contribute to the treatment of fractures, bone delayed unions or nonunions in clinical practice. 相似文献
120.
Mian Cao Zhuo Mao Chuen Kam Nan Xiao Xiaoxing Cao Chong Shen Kenneth K. Y. Cheng Aimin Xu Kwong-Man Lee Liwen Jiang Jun Xia 《PLoS biology》2013,11(4)
Diabetes is a metabolic disorder characterized by hyperglycemia. Insulin, which is secreted by pancreatic beta cells, is recognized as the critical regulator of blood glucose, but the molecular machinery responsible for insulin trafficking remains poorly defined. In particular, the roles of cytosolic factors that govern the formation and maturation of insulin granules are unclear. Here we report that PICK1 and ICA69, two cytosolic lipid-binding proteins, formed heteromeric BAR-domain complexes that associated with insulin granules at different stages of their maturation. PICK1-ICA69 heteromeric complexes associated with immature secretory granules near the trans-Golgi network (TGN). A brief treatment of Brefeldin A, which blocks vesicle budding from the Golgi, increased the amount of PICK1 and ICA69 at TGN. On the other hand, mature secretory granules were associated with PICK1 only, not ICA69. PICK1 deficiency in mice caused the complete loss of ICA69 and led to increased food and water intake but lower body weight. Glucose tolerance tests demonstrated that these mutant mice had high blood glucose, a consequence of insufficient insulin. Importantly, while the total insulin level was reduced in PICK1-deficient beta cells, proinsulin was increased. Lastly, ICA69 knockout mice also displayed similar phenotype as the mice deficient in PICK1. Together, our results indicate that PICK1 and ICA69 are key regulators of the formation and maturation of insulin granules.