全文获取类型
收费全文 | 15274篇 |
免费 | 1463篇 |
国内免费 | 2433篇 |
专业分类
19170篇 |
出版年
2024年 | 70篇 |
2023年 | 285篇 |
2022年 | 673篇 |
2021年 | 1004篇 |
2020年 | 778篇 |
2019年 | 899篇 |
2018年 | 749篇 |
2017年 | 591篇 |
2016年 | 768篇 |
2015年 | 1127篇 |
2014年 | 1368篇 |
2013年 | 1363篇 |
2012年 | 1643篇 |
2011年 | 1584篇 |
2010年 | 953篇 |
2009年 | 812篇 |
2008年 | 896篇 |
2007年 | 763篇 |
2006年 | 620篇 |
2005年 | 483篇 |
2004年 | 362篇 |
2003年 | 320篇 |
2002年 | 230篇 |
2001年 | 102篇 |
2000年 | 108篇 |
1999年 | 114篇 |
1998年 | 86篇 |
1997年 | 72篇 |
1996年 | 57篇 |
1995年 | 47篇 |
1994年 | 42篇 |
1993年 | 30篇 |
1992年 | 32篇 |
1991年 | 33篇 |
1990年 | 23篇 |
1989年 | 17篇 |
1988年 | 13篇 |
1987年 | 7篇 |
1986年 | 4篇 |
1985年 | 19篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 2篇 |
1978年 | 2篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1965年 | 1篇 |
1938年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
21.
Combination of bone tissue engineering and BMP-2 gene transfection promotes bone healing in osteoporotic rats 总被引:12,自引:0,他引:12
OBJECTIVE: The aim of this study was to develop a feasible approach to promote bone healing in osteoporotic rats using autogenous bone tissue-engineering and gene transfection of human bone morphogenetic protein 2 (hBMP-2). METHODS: Bone marrow stromal cells (BMSCs) from the left tibia of osteoporotic rats were transfected with the hBMP-2 gene in vitro which was confirmed by immunohistochemistry, in situ hybridization and Western blotting. Autogenous transfected or untransfected BMSCs were seeded on macroporous coral hydroxyapatite (CHA) scaffolds. Each cell-scaffold construct was implanted into a defect site which was created in the ramus of the mandible of osteoporotic rats. Four or eight weeks after implantation in situ hybridization was performed in BMSCs transfected with hBMP-2, X-ray examinations, histological and histomorphological analyses were used to evaluate the effect of tissue-engineered bone on osseous defect repair. RESULTS: Newly formed bone was observed at the margin of the defect 4 weeks after implantation with BMSCs transfected with BMP-2. Mature bone was observed 8 weeks after treatment. In the control group there was considerably less new bone and some adipose tissue was observed at the defect margins 8 weeks after implantation. CONCLUSIONS: Autogenous cells transfected with hBMP-2 promote bone formation in osteoporotic rats. BMSC-mediated BMP-2 gene therapy used in conjunction with bone tissue engineering may be used to successfully treat bone defects in osteoporotic rats. This method provides a powerful tool for bone regeneration and other tissue engineering. 相似文献
22.
Jin Yan Dong Xing Ping Li Lei Li Guo Hong Li Ya Jun Liu Ke Qin Zhang 《Annals of microbiology》2006,56(2):163-166
One hundred and eighty one fungal species that were isolated from the fresh fruiting bodies collected in the Mountains of Pu Er County of Yunnan Province, China were tested on the pine wood nematode,Bursaphelenchus xylophilus in vitro. Each fungal species was grown in Czapek broth and potato dextrose broth (PDB). Fifteen filtrates fromAmauroderma austrosinense, Amauroderma macer, Filoboletus sp.,Laccaria tortilis, Lactarius gerardii, Lentinula edodes, Oudemansiella longipes, Oudemansiella mucida, Peziza sp.,Pleurotus sp.,Sinotermitomyces carnosus (two strains),Strobilomyces floccopus, Termitomyces albuminosus, Tylopilus striatulus grown on PDB were found to be pathogenic to the tested nematodes. Eleven filtrates fromAmanita junguillea, Amanita sp.,Daedalea sepiaria, Fistulina hepatica, Omphalotus olearius, Oudemansiella mucida, Peziza sp.,Pleurotus pulmatus, Ramaria sp.,Tricholoma conglobatum, Tylopilus striatulus grown on Czapek broth were also pathogenic to the nematodes. When screening for nematicidal potential of fungi, it is important to study the growth medium conditions necessary to obtain the optimal nematicidal effect as fungal filtrates growing on different liquid media showed a very inconsistent toxicity towards nematodes. 相似文献
23.
Antitumor mechanism of Se-containing polysaccharide, a novel organic selenium compound 总被引:1,自引:0,他引:1
Dejing Shang Qiao Cui Yang Li Zhi Yu Lei Wen Yuan Zhao Jianing Zhang 《Frontiers of Biology in China》2009,4(3):248-253
Recent studies on the inhibition of tumor growth by Se-containing polysaccharide were reviewed. Meanwhile, the possible molecular
mechanisms of the inhibition of tumor cell growth through antioxidation, induction of tumor cell apoptosis, blockade of cell
cycle, and enhancement of immunity by Se-containing polysaccharide were proposed. In the end, the potential application of
Se-containing polysaccharide in the prevention and treatment of tumor was elucidated. 相似文献
24.
25.
中国三瘤蝉属一新种(同翅目:蝉科)雷仲仁,李莉(西北农业大学昆虫研究所陕西杨陵712100)作者在进行中国蝉科较系统的分类研究时,发现三瘤蝉属一新种。模式标本保存在西北农业大学昆虫博物馆(正模)和中国科学院动物研究所(副模)。长度单位为mm。穹三瘤蝉... 相似文献
26.
Hepatitis B virus (HBV) core protein (HBc) is a major component of viral nucleocapsid and a multifunctional protein involved
in viral maturation and release. It is unstable and present in cells at low level because of K96 lysine residue, which is
a ubiquitin acceptor site. Np95/ICBP90-like RING finger protein (NIRF) has auto-ubiquitination activity which is the hallmark
of a ubiquitin ligase. In the present study, ubiquitin ligase, NIRF, binds to HBc and leads to the proteasome-mediated degradation
of HBc in vivo. NIRF down-regulates HBc protein level, resulting in the decrease of the amount of HBV particles in supernatant
of HepG2.2.15 cells. However knockdown of NIRF significantly increases endogenous HBc protein level, leading to HBV release.
The results reveal that NIRF interacts with HBc and promotes the degradation of HBc in vivo. The pathway of NIRF-mediated
ubiquitin–proteasome affects the release of HBV particles by controlling the amounts of HBc. It indicates that NIRF may participate
in the maturation of HBV. 相似文献
27.
Sphingosine kinase regulates the sensitivity of Dictyostelium discoideum cells to the anticancer drug cisplatin 下载免费PDF全文
Min J Traynor D Stegner AL Zhang L Hanigan MH Alexander H Alexander S 《Eukaryotic cell》2005,4(1):178-189
The drug cisplatin is widely used to treat a number of tumor types. However, resistance to the drug, which remains poorly understood, limits its usefulness. Previous work using Dictyostelium discoideum as a model for studying drug resistance showed that mutants lacking sphingosine-1-phosphate (S-1-P) lyase, the enzyme that degrades S-1-P, had increased resistance to cisplatin, whereas mutants overexpressing the enzyme were more sensitive to the drug. S-1-P is synthesized from sphingosine and ATP by the enzyme sphingosine kinase. We have identified two sphingosine kinase genes in D. discoideum--sgkA and sgkB--that are homologous to those of other species. The biochemical properties of the SgkA and SgkB enzymes suggest that they are the equivalent of the human Sphk1 and Sphk2 enzymes, respectively. Disruption of the kinases by homologous recombination (both single and double mutants) or overexpression of the sgkA gene resulted in altered growth rates and altered response to cisplatin. The null mutants showed increased sensitivity to cisplatin, whereas mutants overexpressing the sphingosine kinase resulted in increased resistance compared to the parental cells. The results indicate that both the SgkA and the SgkB enzymes function in regulating cisplatin sensitivity. The increase in sensitivity of the sphingosine kinase-null mutants was reversed by the addition of S-1-P, and the increased resistance of the sphingosine kinase overexpressor mutant was reversed by the inhibitor N,N-dimethylsphingosine. Parallel changes in sensitivity of the null mutants are seen with the platinum-based drug carboplatin but not with doxorubicin, 5-fluorouracil, and etoposide. This pattern of specificity is similar to that observed with the S-1-P lyase mutants and should be useful in designing therapeutic schemes involving more than one drug. This study identifies the sphingosine kinases as new drug targets for modulating the sensitivity to platinum-based drugs. 相似文献
28.
Lei Mao Juncai Chen Quanhui Peng Aiming Zhou Zhisheng Wang 《Biological trace element research》2013,155(1):132-141
Zinc has been shown to be an inhibitor of apoptosis for many years. The present study was designed to investigate effects of three zinc chemical forms on H2O2-induced cell apoptosis in IEC-6 cells via analysis of cell vitality, LDH activity, apoptosis percentage, caspase-3 activity, and Bcl-2, Bax, and caspase-3, -8, and -9 gene expression. Cells were divided into H2O2 and zinc sources+H2O2 groups, and there are three different zinc sources [zinc oxide nanoparticle (nano-ZnO), zinc oxide (ZnO), and zinc sulfate (ZnSO4)] and three concentrations (normal = 25 μM, medium = 50 μM, and high = 100 μM) used in this article. In the present study, we found the striking cytotoxicity of H2O2 higher than 200 μM on cell vitality, LDH activity, and apoptosis percentage in the cells using five different concentrations (50, 100, 200, 400, and 800 μM) of H2O2 for 4 h. Moreover, we observed that cell vitality was increased, LDH activity and apoptotic percentage were decreased, and gene expression level of Bax and caspase-3 and -9 was markedly reduced, while gene expression level of Bcl-2 and ratio of Bcl-2/Bax were increased in normal concentration groups of nano-ZnO and ZnSO4 compared with H2O2 group, but no significant difference was observed in caspase-8 gene expression. Furthermore, medium or, more intensely, high concentrations of nano-ZnO and ZnSO4 enhanced H2O2-induced cell apoptosis. Compared with nano-ZnO and ZnSO4, ZnO showed weakest protective effect on H2O2-induced apoptosis at normal concentration and was less toxic to cells at high level. Taken together, we proposed that preventive and protective effects of zinc on H2O2-induced cell apoptosis varied in IEC-6 cells with its chemical forms and concentrations, and maybe for the first time, we suggested that nano-ZnO have a protective effect on H2O2-induced cell apoptosis in IEC-6 cells. 相似文献
29.
30.
Mengchao Yu Jie Lun Hongwei Zhang Lei Wang Gang Zhang Haisheng Zhang Jing Fang 《Acta biochimica et biophysica Sinica》2021,(11):1417-1427
Cancer cells are often exposed to cell intrinsic stresses and environmental perturbations that may lead to accumulation of unfolded and/or misfolded proteins in... 相似文献