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《Expert review of proteomics》2013,10(1):67-75
The rapid expansion of methods for measuring biological data ranging from DNA sequence variations to mRNA expression and protein abundance presents the opportunity to utilize multiple types of information jointly in the study of human health and disease. Organisms are complex systems that integrate inputs at myriad levels to arrive at an observable phenotype. Therefore, it is essential that questions concerning the etiology of phenotypes as complex as common human diseases take the systemic nature of biology into account, and integrate the information provided by each data type in a manner analogous to the operation of the body itself. While limited in scope, the initial forays into the joint analysis of multiple data types have yielded interesting results that would not have been reached had only one type of data been considered. These early successes, along with the aforementioned theoretical appeal of data integration, provide impetus for the development of methods for the parallel, high-throughput analysis of multiple data types. The idea that the integrated analysis of multiple data types will improve the identification of biomarkers of clinical endpoints, such as disease susceptibility, is presented as a working hypothesis. 相似文献
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《Expert review of proteomics》2013,10(2):199-209
Proteomics was initially viewed as a promising new scientific discipline to study complex disorders such as polygenic, infectious and environment-related diseases. However, the first attempts to understand a monogenic disease such as cystic fibrosis (CF) by proteomics-based approaches have proved quite rewarding. In CF, the impairment of a unique protein, the CF transmembrane conductance regulator, does not completely explain the complex and variable CF clinical phenotype. The great advances in our knowledge about the molecular and cellular consequences of such impairment have not been sufficient to be translated into effective treatments, and CF patients are still dying due to chronic progressive lung dysfunction. The progression of proteomics application in CF will certainly unravel new proteins that could be useful as biomarkers either to elucidate CF basic mechanisms and to better monitor the disease progression, or to promote the development of novel therapeutic strategies against CF. This review will summarize the recent technological advances in proteomics and the first results of its application to address the most important issues in the CF field. 相似文献
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Mei Zeng Baofeng Chen Yufeng Qing Wenguang Xie Wantai Dang Mingcai Zhao 《Nucleosides, nucleotides & nucleic acids》2013,32(7):455-465
Glut9 is highly expressed in the human kidney proximal convoluted tubular and plays a crucial role in the regulation of plasma urate levels. The gene effects were stronger among women. Our results show that 17-β-estradiol (E2) through ER (estrogen receptor) β downregulates Glut9 protein expression on human renal tubular epithelial cell line (HK2). Intriguingly, E2 does not affect the expression of Glut9 mRNA. ERβ is linked to PTEN, the PTEN gene negatively regulates the PI3K/AKT pathway, and the PI3K/AKT pathway inhibition may lead to autophagy. Further study indicates that ERβ may affect the expression of Glut9 though autophagy. 相似文献
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《Biomarkers》2013,18(5):425-435
AbstractData from 30 pharmacogenomic studies that investigated MDR1 mRNA expression or gene variants (C3435T, G2677TA, C1236T) and response to therapy in acute myeloid leukaemia (AML) were synthesized. Anthracycline-based regimens were mainly used. MDR1 mRNA overexpression was associated with poor response to therapy [odds ratio (OR)?=?2.49 95% confidence interval (CI) 1.38–4.50]. The gene variants were not associated with response to treatment; the generalized ORs, a genetic model-free approach, for the variants C3435T, G2677TA and C1236T were ORG?=?0.86 (95% CI 0.55–1.37), ORG?=?0.97 (95% CI 0.58–1.64) and ORG?=?1.17 (95% CI 0.75--1.83), respectively. There is indication that MDR1 mRNA expression may be considered as a potential marker for response to chemotherapy in AML patients. 相似文献
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Shuguang Leng Juan Cheng Zufei Pan Chuanfeng Huang Yong Niu Yufei Dai 《Biomarkers》2013,18(4-5):395-406
A wide variety of base damages and single-strand breaks formed by reactive oxygen species during metabolic activation of polycyclic aromatic hydrocarbons (PAHs) have been recognized to be involved in PAH carcinogenesis. In this study, alkaline comet assay was used to detect the DNA damage in peripheral blood lymphocytes among 143 coke-oven workers and 50 non-coke-oven workers, and the effects of genetic polymorphisms of XRCC1 and ERCC2 genes on DNA damage were evaluated. The olive tail moment was significantly higher in coke-oven workers than in non-coke-oven workers (2.6, 95% CI=2.1–3.3 versus 1.0, 95% CI=0.8–1.2, p<0.01), and significant correlation between ln-transformed urinary 1-OHP and ln-transformed olive tail moment was found in total population (n=193, Pearson's r=0.393, p<0.001) and in coke-oven workers (n=143, Pearson's r=0.224, p=0.007). The olive tail moment was significantly higher in coke-oven workers with GA genotype of G27466A polymorphism of XRCC1 than those with GG genotype (4.6, 95% CI=2.5–8.7 versus 2.4, 95% CI=1.9–2.9, p<0.01 with adjustment for covariates). No significant associations between C26304T, G28152A and G36189A polymorphisms of XRCC1 and G23591A and A35931C polymorphisms of ERCC2 and olive tail moment were found in both groups. The study showed that the alkaline comet assay is a suitable biomarker in the detection of DNA damage among coke-oven workers and it suggested that the A allele of G27466A polymorphism of XRCC1 may be associated with decreased DNA repair capacity toward PAH-induced base damage and strand breaks. 相似文献
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