全文获取类型
收费全文 | 14195篇 |
免费 | 1357篇 |
国内免费 | 2201篇 |
出版年
2024年 | 50篇 |
2023年 | 240篇 |
2022年 | 587篇 |
2021年 | 922篇 |
2020年 | 726篇 |
2019年 | 842篇 |
2018年 | 713篇 |
2017年 | 561篇 |
2016年 | 719篇 |
2015年 | 1043篇 |
2014年 | 1272篇 |
2013年 | 1263篇 |
2012年 | 1559篇 |
2011年 | 1490篇 |
2010年 | 895篇 |
2009年 | 757篇 |
2008年 | 834篇 |
2007年 | 701篇 |
2006年 | 571篇 |
2005年 | 434篇 |
2004年 | 319篇 |
2003年 | 285篇 |
2002年 | 205篇 |
2001年 | 94篇 |
2000年 | 102篇 |
1999年 | 104篇 |
1998年 | 77篇 |
1997年 | 60篇 |
1996年 | 53篇 |
1995年 | 43篇 |
1994年 | 39篇 |
1993年 | 25篇 |
1992年 | 31篇 |
1991年 | 33篇 |
1990年 | 22篇 |
1989年 | 16篇 |
1988年 | 12篇 |
1987年 | 7篇 |
1986年 | 4篇 |
1985年 | 20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
911.
912.
Soluble production and function of vascular endothelial growth factor/basic fibroblast growth factor complex peptide
下载免费PDF全文
![点击此处可从《Biotechnology progress》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Qing Zhang Zhongsong Zhu Lei Pang Yong Tang Qifang Song Jiangfang Huang Jie Deng Ning Deng Qin Yang Aditi M. Sengupta Likuan Xiong 《Biotechnology progress》2015,31(1):194-203
Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are important proangiogenic factors in tumor procession. The autocrine and paracrine bFGF and the VEGF in tumor tissue can promote tumor angiogenesis, tumor growth, and metastasis. A VEGF/bFGF Complex Peptide (VBP3) was designed on the basis of epitope peptides from both VEGF and bFGF to elicit in vivo production of anti‐bFGF and anti‐VEGF antibodies. In this study, we reported on the production of recombinant VBP3 using high cell density fermentation. Fed‐batch fermentation for recombinant VBP3 production was conducted, and the production procedure was optimized in a 10‐L fermentor. The fraction of soluble VBP3 protein obtained reached 78% of total recombinant protein output under fed‐batch fermentation. Purified recombinant VBP3 could inhibit tumor cell proliferation in vitro and stimulate C57BL/6 mice to produce high titer anti‐VEGF and anti‐bFGF antibodies in vivo. A melanoma‐grafted mouse model and an immunohistochemistry assay showed that tumor growth and tumor angiogenesis were significantly inhibited in VBP3‐vaccinated mice. These results demonstrated that soluble recombinant VBP3 could be produced by large‐scale fermentation, and the product, with good immunogenicity, elicited production of high‐titer anti‐bFGF and anti‐VEGF antibodies, which could be used as a therapeutic tumor vaccine to inhibit tumor angiogenesis and tumor growth. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 31:194–203, 2015 相似文献
913.
Yi-lun Wang Chao Zeng Jie Wei Tuo Yang Hui Li Zhen-han Deng Ye Yang Yi Zhang Xiang Ding Dong-xing Xie Tu-bao Yang Guang-hua Lei 《PloS one》2015,10(11)
Objective
To examine the cross-sectional associations between dietary magnesium (Mg) intake and hyperuricemia (HU).Methods
5168 subjects were included in this study. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire. Hyperuricemia (HU) was defined as uric acid ≥ 416 μmol/L for male population and ≥ 360 μmol/L for female. A multivariable logistic analysis model was applied to test the associations after adjusting a number of potential confounding factors.Results
The relative odds of the overall prevalence of HU were decreased by 0.57 times in the fourth quintile of Mg intake (OR 0.57, 95% CI 0.35–0.94) and 0.55 times in the fifth quintile (OR 0.55, 95% CI 0.30–1.01) comparing with the lowest quintile, and P for trend was 0.091. The results of multivariable linear regression also suggested a significant inverse association between serum uric acid and Mg intake (β = -0.028, P = 0.022). For male, the relative odds of HU were decreased by 0.62 times in the third quintile of Mg intake (OR 0.62, 95% CI 0.40–0.97), 0.40 times in the fourth quintile (OR 0.40, 95% CI 0.23–0.72) and 0.35 times in the fifth quintile (OR 0.35, 95% CI 0.17–0.71) comparing with the lowest quintile, and P for trend was 0.006. Multivariable adjusted inverse association was also existed between serum uric acid and Mg intake in male population (β = -0.061, P = 0.002). However, no significant association was observed between dietary Mg intake and HU for female.Conclusions
The findings of this cross-sectional study indicated that dietary Mg intake is inversely associated with HU, independent of some major confounding factors. In addition, this association remains valid for the male subgroup, but not for the female subgroup.Level of Evidence
LevelIII, cross-sectional study. 相似文献914.
Min Chen Wenjing Tang Lei Hou Ruozhuo Liu Zhao Dong Xun Han Xiaofei Zhang Dongjun Wan Shengyuan Yu 《PloS one》2015,10(6)
Background and Objective
Conflicting data have been reported on the association between tumor necrosis factor (TNF) –308G>A and nitric oxide synthase 3 (NOS3) +894G>T polymorphisms and migraine. We performed a meta-analysis of case-control studies to evaluate whether the TNF –308G>A and NOS3 +894G>T polymorphisms confer genetic susceptibility to migraine.Method
We performed an updated meta-analysis for TNF –308G>A and a meta-analysis for NOS3 +894G>T based on studies published up to July 2014. We calculated study specific odds ratios (OR) and 95% confidence intervals (95% CI) assuming allele contrast, dominant model, recessive model, and co-dominant model as pooled effect estimates.Results
Eleven studies in 6682 migraineurs and 22591 controls for TNF –308G>A and six studies in 1055 migraineurs and 877 controls for NOS3 +894G>T were included in the analysis. Neither indicated overall associations between gene polymorphisms and migraine risk. Subgroup analyses suggested that the “A” allele of the TNF –308G>A variant increases the risk of migraine among non-Caucasians (dominant model: pooled OR = 1.82; 95% CI 1.15 – 2.87). The risk of migraine with aura (MA) was increased among both Caucasians and non-Caucasians. Subgroup analyses suggested that the “T” allele of the NOS3 +894G>T variant increases the risk of migraine among non-Caucasians (co-dominant model: pooled OR = 2.10; 95% CI 1.14 – 3.88).Conclusions
Our findings appear to support the hypothesis that the TNF –308G>A polymorphism may act as a genetic susceptibility factor for migraine among non-Caucasians and that the NOS3 +894G>T polymorphism may modulate the risk of migraine among non-Caucasians. 相似文献915.
Cheryl Carson Pichai Raman Jennifer Tullai Lei Xu Martin Henault Emily Thomas Sarita Yeola Jianmin Lao Mark McPate J. Martin Verkuyl George Marsh Jason Sarber Adam Amaral Scott Bailey Danuta Lubicka Helen Pham Nicolette Miranda Jian Ding Hai-Ming Tang Haisong Ju Pamela Tranter Nan Ji Philipp Krastel Rishi K. Jain Andrew M. Schumacher Joseph J. Loureiro Elizabeth George Giuliano Berellini Nathan T. Ross Simon M. Bushell Gül Erdemli Jonathan M. Solomon 《PloS one》2015,10(6)
Englerin A is a structurally unique natural product reported to selectively inhibit growth of renal cell carcinoma cell lines. A large scale phenotypic cell profiling experiment (CLiP) of englerin A on ¬over 500 well characterized cancer cell lines showed that englerin A inhibits growth of a subset of tumor cell lines from many lineages, not just renal cell carcinomas. Expression of the TRPC4 cation channel was the cell line feature that best correlated with sensitivity to englerin A, suggesting the hypothesis that TRPC4 is the efficacy target for englerin A. Genetic experiments demonstrate that TRPC4 expression is both necessary and sufficient for englerin A induced growth inhibition. Englerin A induces calcium influx and membrane depolarization in cells expressing high levels of TRPC4 or its close ortholog TRPC5. Electrophysiology experiments confirmed that englerin A is a TRPC4 agonist. Both the englerin A induced current and the englerin A induced growth inhibition can be blocked by the TRPC4/C5 inhibitor ML204. These experiments confirm that activation of TRPC4/C5 channels inhibits tumor cell line proliferation and confirms the TRPC4 target hypothesis generated by the cell line profiling. In selectivity assays englerin A weakly inhibits TRPA1, TRPV3/V4, and TRPM8 which suggests that englerin A may bind a common feature of TRP ion channels. In vivo experiments show that englerin A is lethal in rodents near doses needed to activate the TRPC4 channel. This toxicity suggests that englerin A itself is probably unsuitable for further drug development. However, since englerin A can be synthesized in the laboratory, it may be a useful chemical starting point to identify novel modulators of other TRP family channels. 相似文献
916.
Porous microcarriers were fabricated from synthesized poly(γ-benzyl-L-glutamate) (PBLG) polymer to engineer adipose tissue with lobule-like structure via the injectable approach. The adipogenic differentiation of human adipose-derived stem cells (hASCs) seeded on porous PBLG microcarriers was determined by adipogenic gene expression and glycerol-3-phosphate dehydrogenase enzyme activity. In vitro adipogenic cultivation was performed for 7 days, and induced hASC/PBLG complex (Adi-ASC/PBLG group) was subcutaneously injected into nude mice. Injections of PBLG microcarriers alone (PBLG group) and non-induced hASC/PBLG complex (ASC/PBLG group) served as controls. Newly formed tissues were harvested after 4 and 8 weeks. Generation of subcutaneous adipose tissue with typical lobule-like structure separated by fibrous septa was observed upon injection of adipogenic-induced hASC/microsphere complex. Adipogenesis significantly increased in the Adi-ASC/PBLG group compared with the control groups. The angiogenesis in the engineered adipose tissue was comparable to that in normal tissue as determined by capillary density and luminal diameter. Cell tracking assay demonstrated that labeled hASCs remained detectable in the neo-generated tissues 8 weeks post-injection using green fluorescence protein-labeled hASCs. These results indicate that adipose tissue with typical lobule-like structure could be engineered using injectable porous PBLG microspheres loaded with adipogenic-induced hASCs. 相似文献
917.
Zhaowei Teng Yun Zhu Feihu Wu Yanhong Zhu Xiguang Zhang Chuanlin Zhang Shuangneng Wang Lei Zhang 《PloS one》2015,10(6)
Objective
To evaluate the association between chronic opioid use for non-cancer pain and fracture risk by conducting a meta-analysis of cohort studies.Methods
Cohort studies were identified by searching PubMed and EMBASE from their inception to July 2014. A fracture was considered an endpoint. The information was extracted by two authors independently. When the heterogeneity was significant, a random-effects model was used to calculate the overall pooled risk estimates.Results
Eight cohort studies were included in the final meta-analysis. On the basis of the Newcastle-Ottawa Scale (NOS), six studies were considered to be of high quality. The overall combined relative risk for the use of opioids and fractures was 1.88 (95% confidence interval [CI] 1.51-2.34). A subgroup analysis revealed the sources of heterogeneity. The sensitivity analysis indicated stable results, and no publication bias was observed.Conclusions
This meta-analysis of cohort studies demonstrates that opioids significantly increase the risk of fractures. 相似文献918.
Background and Aim
Several studies have been conducted to examine the associations between osteopontin (OPN) promoter gene SPP1 polymorphisms with human cancers in Chinese population, but the results remain inconsistent. The aim of this meta-analysis is to clarify the associations between SPP1 polymorphisms and cancer susceptibility.Methods
All eligible case-control studies published up to March 2015 were identified by searching PubMed, Web of Science, Embase, and Cochrane Library without language restrictions. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated using fixed- or random-effect model.Results
A total of 11 case-control studies were included; of those, there were eleven studies (3130 cases and 3828 controls) for -443T>C polymorphism, ten studies (3019 cases and 3615 controls) for -156G>GG polymorphism, eight studies (2258 cases and 2846 controls) for -66T>G polymorphism. Overall, no evidence indicated that the -443 T>C polymorphism was associated with cancer risk (OR = 0.93, 95%CI 0.62–1.38 for dominant model, OR = 1.06, 95%CI 0.73–1.55 for recessive model, OR = 0.88, 95%CI 0.62–1.26 for CT vs TT model, OR = 1.03, 95%CI 0.61–1.73 for CC vs TT model). While, a significantly increase risk was found for -156 G>GG polymorphism (OR = 1.22, 95%CI 1.10–1.35 for dominant model, OR = 1.25, 95%CI 1.10–1.41 for recessive model, OR = 1.18, 95%CI 1.06–1.32 for GGG vs GG model, OR = 1.35, 95%CI 1.09–1.68 for GGGG vs GG model). For -66T>G polymorphism, we found a decrease risk of cancer (OR = 0.84, 95% CI 0.71–0.98 for dominant model), but this result changed (OR = 0.93, 95% CI 0.77–1.12 for dominant model) when we excluded a study.Conclusion
This meta-analysis suggests that in Chinese population the -156G>GG polymorphism of SPP1 might be a risk factor for human cancers, while -443T>C mutation is not associated with cancer risk. For -66T>G polymorphism, it may be a protective factor for human cancers. 相似文献919.
K. Huang K. Bi C. Liang S. Lin W. J. Wang T. Z. Yang J. Liu R. Zhang D. Y. Fan Y. G. Wang M. Lei 《PloS one》2015,10(9)
Novel graphite-molybdenum carbide nanocomposites (G-Mo2C) are synthesized by a typical solid state reaction with melamine and MoO3 as precursors under inert atmosphere. The characterization results indicate that G-Mo2C composites are composed of high crystallization and purity of Mo2C and few layers of graphite carbon. Mo2C nanoparticles with sizes ranging from 5 to 50 nm are uniformly supported by surrounding graphite layers. It is believed that Mo atom resulting from the reduction of MoO3 is beneficial to the immobilization of graphite carbon. Moreover, the electrocatalytic performances of G-Mo2C for ORR in alkaline medium are investigated by cyclic voltammetry (CV), rotating disk electrode (RDE) and chronoamperometry test with 3M methanol. The results show that G-Mo2C has a considerable catalytic activity and superior methanol tolerance performance for the oxygen reduction reaction (ORR) benefiting from the chemical interaction between the carbide nanoparticles and graphite carbon. 相似文献
920.
Ying Si Soojin Kim Xiangqin Cui Lei Zheng Shin J. Oh Tina Anderson Mohammad AlSharabati Mohamed Kazamel Laura Volpicelli-Daley Marcas M. Bamman Shaohua Yu Peter H. King 《PloS one》2015,10(9)
We recently identified Smads1, 5 and 8 as muscle biomarkers in human ALS. In the ALS mouse, these markers are elevated and track disease progression. Smads are signal transducers and become activated upon receptor engagement of ligands from the TGF-β superfamily. Here, we sought to characterize ligands linked to activation of Smads in ALS muscle and their role as biomarkers of disease progression. RNA sequencing data of ALS muscle samples were mined for TGF-β superfamily ligands. Candidate targets were validated by qRT-PCR in a large cohort of human ALS muscle biopsy samples and in the G93A SOD1 mouse. Protein expression was evaluated by Western blot, ELISA and immunohistochemistry. C2C12 muscle cells were used to assess Smad activation and induction. TGF-β1, 2 and 3 mRNAs were increased in ALS muscle samples compared to controls and correlated with muscle strength and Smads1, 2, 5 and 8. In the G93A SOD1 mouse, the temporal pattern of TGF-β expression paralleled the Smads and increased with disease progression. TGF-β1 immunoreactivity was detected in mononuclear cells surrounding muscle fibers in ALS samples. In muscle cells, TGF-β ligands were capable of activating Smads. In conclusion, TGF-β1, 2 and 3 are novel biomarkers of ALS in skeletal muscle. Their correlation with weakness in human ALS and their progressive increase with advancing disease in the ALS mouse suggest that they, as with the Smads, can track disease progression. These ligands are capable of upregulating and activating Smads and thus may contribute to the Smad signaling pathway in ALS muscle. 相似文献