全文获取类型
收费全文 | 56372篇 |
免费 | 4797篇 |
国内免费 | 4287篇 |
出版年
2023年 | 682篇 |
2022年 | 848篇 |
2021年 | 2846篇 |
2020年 | 2074篇 |
2019年 | 2497篇 |
2018年 | 2339篇 |
2017年 | 1804篇 |
2016年 | 2544篇 |
2015年 | 3627篇 |
2014年 | 4379篇 |
2013年 | 4435篇 |
2012年 | 5286篇 |
2011年 | 4762篇 |
2010年 | 2882篇 |
2009年 | 2598篇 |
2008年 | 2937篇 |
2007年 | 2634篇 |
2006年 | 2261篇 |
2005年 | 1886篇 |
2004年 | 1509篇 |
2003年 | 1420篇 |
2002年 | 1072篇 |
2001年 | 910篇 |
2000年 | 886篇 |
1999年 | 797篇 |
1998年 | 487篇 |
1997年 | 446篇 |
1996年 | 462篇 |
1995年 | 422篇 |
1994年 | 413篇 |
1993年 | 326篇 |
1992年 | 446篇 |
1991年 | 324篇 |
1990年 | 284篇 |
1989年 | 260篇 |
1988年 | 210篇 |
1987年 | 194篇 |
1986年 | 176篇 |
1985年 | 154篇 |
1984年 | 115篇 |
1983年 | 122篇 |
1982年 | 81篇 |
1981年 | 45篇 |
1980年 | 51篇 |
1979年 | 63篇 |
1977年 | 34篇 |
1976年 | 46篇 |
1974年 | 54篇 |
1973年 | 45篇 |
1972年 | 53篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
991.
992.
Growth differentiation factor 15 (GDF15), a direct target gene of p53, is a multifunctional member of the TGF-β/BMP superfamily. GDF15 can be induced and is implicated as a key secretory cytokine in response to multiple cellular stimuli. Accumulating evidence indicates that GDF15 is associated with the development and prognosis of diabetes mellitus, while whether GDF15 can be induced by high glucose is unknown. In the present study, we revealed that high glucose could induce GDF15 expression and secretion in cultured human umbilical vein endothelial cells in a ROS- and p53-dependent manner. Inhibition of high glucose-induced GDF15 expression by siRNA demonstrated that adaptively induced GDF15 played a protective role against high glucose-induced human umbilical vein endothelial cell apoptosis via maintaining the active state of PI3K/Akt/eNOS pathway and attenuating NF-κB/JNK pathway activation. The protective effects of GDF15 were probably achieved by inhibiting ROS overproduction in high glucose-treated human umbilical vein endothelial cells in a negative feedback manner. Our results suggest that high glucose can promote GDF15 expression and secretion in human umbilical vein endothelial cells, which in turn attenuates high glucose-induced endothelial cell apoptosis. 相似文献
993.
994.
MiRNAs are a class of non-coding small RNAs that play important roles in the regulation of gene expression. Although plant miRNAs have been extensively studied in model systems, less is known in other plants with limited genome sequence data, including eggplant (Solanum melongena L.). To identify miRNAs in eggplant and their response to Verticillium dahliae infection, a fungal pathogen for which clear understanding of infection mechanisms and effective cure methods are currently lacking, we deep-sequenced two small RNA (sRNA) libraries prepared from mock-infected and infected seedlings of eggplants. Specifically, 30,830,792 reads produced 7,716,328 unique miRNAs representing 99 known miRNA families that have been identified in other plant species. Two novel putative miRNAs were predicted with eggplant ESTs. The potential targets of the identified known and novel miRNAs were also predicted based on sequence homology search. It was observed that the length distribution of obtained sRNAs and the expression of 6 miRNA families were obviously different between the two libraries. These results provide a framework for further analysis of miRNAs and their role in regulating plant response to fungal infection and Verticillium wilt in particular. 相似文献
995.
Yang Jiang Bi-Qing Li Yuchao Zhang Yuan-Ming Feng Yu-Fei Gao Ning Zhang Yu-Dong Cai 《PloS one》2013,8(6)
Most of pyruvoyl-dependent proteins observed in prokaryotes and eukaryotes are critical regulatory enzymes, which are primary targets of inhibitors for anti-cancer and anti-parasitic therapy. These proteins undergo an autocatalytic, intramolecular self-cleavage reaction in which a covalently bound pyruvoyl group is generated on a conserved serine residue. Traditional detections of the modified serine sites are performed by experimental approaches, which are often labor-intensive and time-consuming. In this study, we initiated in an attempt for the computational predictions of such serine sites with Feature Selection based on a Random Forest. Since only a small number of experimentally verified pyruvoyl-modified proteins are collected in the protein database at its current version, we only used a small dataset in this study. After removing proteins with sequence identities >60%, a non-redundant dataset was generated and was used, which contained only 46 proteins, with one pyruvoyl serine site for each protein. Several types of features were considered in our method including PSSM conservation scores, disorders, secondary structures, solvent accessibilities, amino acid factors and amino acid occurrence frequencies. As a result, a pretty good performance was achieved in our dataset. The best 100.00% accuracy and 1.0000 MCC value were obtained from the training dataset, and 93.75% accuracy and 0.8441 MCC value from the testing dataset. The optimal feature set contained 9 features. Analysis of the optimal feature set indicated the important roles of some specific features in determining the pyruvoyl-group-serine sites, which were consistent with several results of earlier experimental studies. These selected features may shed some light on the in-depth understanding of the mechanism of the post-translational self-maturation process, providing guidelines for experimental validation. Future work should be made as more pyruvoyl-modified proteins are found and the method should be evaluated on larger datasets. At last, the predicting software can be downloaded from http://www.nkbiox.com/sub/pyrupred/index.html. 相似文献
996.
Pengchao Li Jinbao Gu Xiao Yang Hongzhou Cai Jun Tao Xuejian Yang Qiang Lu Zengjun Wang Changjun Yin Min Gu 《PloS one》2013,8(8)
Background
A functional -94 insertion/deletion polymorphism (rs28362491) in the promoter of the NFKB1 gene was reported to influence NFKB1 expression and confer susceptibility to different types of cancer. This study aims to determine whether the polymorphism is associated with risk of bladder cancer.Materials and methods
TaqMan assay was used to determine genotype among 609 cases and 640 controls in a Chinese population. Logistic regression was used to assess the association between the polymorphism and bladder cancer risk, and quantitative real-time polymerase chain reaction was used to determine NFKB1 mRNA expression.Results
Compared with the ins/ins/ins/del genotypes, the del/del genotype was associated with a significantly increased risk of bladder cancer [adjusted odd ratio (OR) = 1.92, 95% confidence interval (CI) = 1.42–2.59]. The increased risk was more prominent among subjects over 65 years old (OR = 2.37, 95% CI = 1.52–3.70), male subjects (OR = 1.97, 95% CI = 1.40–2.79) and subjects with self-reported family history of cancer (OR = 3.59, 95% CI = 1.19–10.9). Furthermore, the polymorphism was associated with a higher risk of developing non-muscle invasive bladder cancer (OR = 2.07, 95% CI = 1.51–2.85), grade 1 bladder cancer (OR = 2.40, 95% CI = 1.68–3.43), single tumor bladder cancer (OR = 2.04, 95% CI = 1.48–2.82) and smaller tumor size bladder cancer (OR = 2.10, 95% CI = 1.51–2.92). The expression of NFKB1 mRNA in bladder cancer tissues with homozygous insertion genotype was higher than that with deletion allele.Conclusions
In conclusion, the -94 ins/del ATTG polymorphism in NFKB1 promoter may contribute to the etiology of bladder cancer in the Chinese population. 相似文献997.
Yun-Song Wang Rong Huang Yan Li Wen-Bin Shang Fei Chen Hong-Bin Zhang Jing-Hua Yang 《Phytochemistry letters》2013,6(1):26-30
A pair of novel tetrahydrobenzofuran derivatives with a unique C18 carbon skeleton, panamonon A (1) and B (2), was isolated from the leaves and twigs of Litsea panamonja (Nees) Hook. f. These new compounds contain an unprecedented C18 carbon skeleton consisting of a characteristic tetrahydrobenzofuran-2,5(3H,6H)-dione core with a biosynthetically extended geranyl side chain, designated as “panamonane”.Highlights? A pair of novel tetrahydrobenzofuran derivatives with a unique C18 carbon skeleton was isolated. ? The new compounds possess an unprecedented C18 carbon skeleton and are designated as “panamonane”. ? They are featured with a tetrahydrobenzofuran-2,5(3H,6H)-dione moiety and a geranyl side chain. ? The plausible biosynthetic pathways of them were discussed. 相似文献
998.
Wei Zhao Xiaoying Zeng Tao Zhang Lan Wang Guangyu Yang Yong-Kuan Chen Qiufen Hu Mingming Miao 《Phytochemistry letters》2013,6(2):179-182
Two new flavonoids, fistulaflavonoids B and C (1–2), together with five known flavonoids (3–7) were isolated from the bark and stems of Cassia fistula. Their structures were determined by means of HRESIMS, extensive 1D and 2D NMR spectroscopic studies and chemical evidences. The anti-tobacco mosaic virus (anti-TMV) activity of the isolated flavonoids was also evaluated. The results showed that compounds 1 and 2 showed high anti-TMV activity with inhibition rate of 28.5% and 31.3%, which is higher than that of Ningnanmycin (24.7%). Compounds 4–7 showed modest anti-TMV activity with inhibition rate of 18.5%, 22.7%, 16.4%, and 15.3%, respectively. 相似文献
999.
Guoxu Ma Haifeng Wu Jingquan Yuan Lizhen Wu Qingxia Zheng Zhaocui Sun Xiaoru Fan Hua Wei Junshan Yang Xudong Xu 《Phytochemistry letters》2013,6(1):152-155
Five phenylpropanoids including one new compound balanophonin A (1), one new natural compound balanophonin B (2) were isolated from the seeds of Lithocarpus pachylepis for the first time. Their structures were elucidated by various spectroscopic techniques (UV, IR, MS, CD, 1D and 2D NMR). All compounds were evaluated for their anti-inflammatory activities on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7. 相似文献
1000.
Antibody-based immunotherapy has been effectively used for tumor treatment. However, to date, only a few tumor-associated antigens (TAAs) or therapeutic targets have been identified. Identification of more immunogenic antigens is essential for improvements in multiple myeloma (MM) diagnosis and therapy. In this study, we synthesized a polyclonal antibody (PAb) by immunizing rabbits with whole human plasmacytoma ARH-77 cells and identified MM-associated antigens, including enlonase, adipophilin, and HSP90s, among others, via proteomic technologies. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that 200 µg/mL PAb inhibits the proliferation of ARH-77 cells by over 50% within 48 h. Flow cytometric assay indicated that PAb treatment significantly increases the number of apoptotic cells compared with other treatments (52.1% vs. NS, 7.3% or control rabbit IgG, 9.9%). In vivo, PAb delayed tumor growth and prolonged the lifespan of mice. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that PAb also induces statistically significant changes in apoptosis compared with other treatments (P<0.05). We therefore conclude that PAb could be used for the effective screening and identification of TAA. PAb may have certain anti-tumor functions in vitro and in vivo. As such, its combination with proteomic technologies could be a promising approach for sieving TAA for the diagnosis and therapy of MM. 相似文献