全文获取类型
收费全文 | 2205篇 |
免费 | 219篇 |
国内免费 | 1篇 |
专业分类
2425篇 |
出版年
2023年 | 4篇 |
2022年 | 15篇 |
2021年 | 36篇 |
2020年 | 21篇 |
2019年 | 29篇 |
2018年 | 24篇 |
2017年 | 30篇 |
2016年 | 66篇 |
2015年 | 89篇 |
2014年 | 84篇 |
2013年 | 114篇 |
2012年 | 185篇 |
2011年 | 167篇 |
2010年 | 110篇 |
2009年 | 75篇 |
2008年 | 173篇 |
2007年 | 156篇 |
2006年 | 157篇 |
2005年 | 137篇 |
2004年 | 124篇 |
2003年 | 120篇 |
2002年 | 160篇 |
2001年 | 30篇 |
2000年 | 23篇 |
1999年 | 31篇 |
1998年 | 42篇 |
1997年 | 12篇 |
1996年 | 16篇 |
1995年 | 17篇 |
1994年 | 21篇 |
1993年 | 14篇 |
1992年 | 18篇 |
1991年 | 13篇 |
1990年 | 8篇 |
1989年 | 7篇 |
1988年 | 6篇 |
1987年 | 8篇 |
1986年 | 7篇 |
1985年 | 7篇 |
1984年 | 5篇 |
1983年 | 5篇 |
1982年 | 9篇 |
1981年 | 8篇 |
1980年 | 12篇 |
1979年 | 5篇 |
1978年 | 3篇 |
1977年 | 5篇 |
1976年 | 5篇 |
1975年 | 4篇 |
1967年 | 2篇 |
排序方式: 共有2425条查询结果,搜索用时 0 毫秒
91.
Macpherson CC 《Bioethics》2004,18(3):283-292
CIOMS has been criticised for not adequately consulting stakeholders about its revised ethical guidelines regarding medical research. Political and logistical issues that arise in democratic processes and open exchange of information probably contributed to this exclusion. What might CIOMS have done to be more inclusive and attain broader consensus on its proposed revisions? Consensus is dynamic, and evolves as a community digests new information and perspectives. Engaging the public (and particularly the stakeholders) in discussion about the revisions would have generated broader consensus. It would have encouraged more stakeholders (i.e. researchers, potential research participants, research institutions, or governments) to buy in. CIOMS needs a process to encourage dialogue and stakeholder input. The CIOMS guidelines themselves promote stakeholder consultation and capacity building, but CIOMS has done relatively little to distribute or promote its own guidelines. CIOMS should do more to promote its revised guidelines, and engage stakeholders in dialogue. This paper explores the bioethics debate about universal and relative values to illustrate the value of consultation and consensus building. It concludes that like research sponsors, CIOMS and similar organisations have an ethical responsibility to facilitate capacity building in less developed areas, and to participate more actively in consensus building. 相似文献
92.
Genomewide linkage searches for Mendelian disease loci can be efficiently conducted using high-density SNP genotyping arrays 总被引:5,自引:0,他引:5 下载免费PDF全文
Sellick GS Longman C Tolmie J Newbury-Ecob R Geenhalgh L Hughes S Whiteford M Garrett C Houlston RS 《Nucleic acids research》2004,32(20):e164
Genomewide linkage searches aimed at identifying disease susceptibility loci are generally conducted using 300–400 microsatellite markers. Genotyping bi-allelic single nucleotide polymorphisms (SNPs) provides an alternative strategy. The availability of dense SNP maps coupled with recent technological developments in highly paralleled SNP genotyping makes it practical to now consider the use of these markers for whole-genome genetic linkage analyses. Here, we report the findings from three successful genomewide linkage analyses of families segregating autosomal recessively inherited neonatal diabetes, craniosynostosis and dominantly inherited renal dysplasia using the Affymetrix 10K SNP array. A single locus was identified for each disease state, two of which are novel. The performance of the SNP array, both in terms of efficiency and precision, indicates that such platforms will become the dominant technology for performing genomewide linkage searches. 相似文献
93.
94.
Amegbey G Chang Z Stothard P Yee A Arrowsmith C Wishart DS 《Journal of biomolecular NMR》2004,30(4):459-460
95.
96.
Kerfeld CA 《Photosynthesis research》2004,81(3):215-225
The orange carotenoid protein (OCP) and its derivative, the red carotenoid protein (RCP), appear to play important photoprotective roles in cyanobacteria. Structural and functional characterization is gradually elucidating the specific details of how carotenoid-protein interactions, including the role of six methionine residues oriented toward the pigment, contribute to the spectral and functional properties of these proteins. 相似文献
97.
Hangeland JJ Doweyko AM Dejneka T Friends TJ Devasthale P Mellström K Sandberg J Grynfarb M Sack JS Einspahr H Färnegårdh M Husman B Ljunggren J Koehler K Sheppard C Malm J Ryono DE 《Bioorganic & medicinal chemistry letters》2004,14(13):3549-3553
A set of thyromimetics having improved selectivity for TR-beta1 were prepared by replacing the 3'-isopropyl group of 2 and 3 with substituents having increased steric bulk. From this limited SAR study, the most potent and selective compounds identified were derived from 2 and contained a 3'-phenyl moiety bearing small hydrophobic groups meta to the biphenyl link. X-ray crystal data of 15c complexed with TR-beta1 LBD shows methionine 442 to be displaced by the bulky R3' phenyl ethyl amide side chain. Movement of this amino acid side chain provides an expanded pocket for the bulky side chain while the ligand-receptor complex retains full agonist activity. 相似文献
98.
Structural proteomics: a tool for genome annotation 总被引:1,自引:0,他引:1
Yakunin AF Yee AA Savchenko A Edwards AM Arrowsmith CH 《Current opinion in chemical biology》2004,8(1):42-48
In any newly sequenced genome, 30% to 50% of genes encode proteins with unknown molecular or cellular function. Fortunately, structural genomics is emerging as a powerful approach of functional annotation. Because of recent developments in high-throughput technologies, ongoing structural genomics projects are generating new structures at an unprecedented rate. In the past year, structural studies have identified many new structural motifs involved in enzymatic catalysis or in binding ligands or other macromolecules (DNA, RNA, protein). The efficiency by which function is deduced from structure can be further improved by the integration of structure with bioinformatics and other experimental approaches, such as screening for enzymatic activity or ligand binding. 相似文献
99.
Comparison of the epidemiology, drug resistance mechanisms, and virulence of Candida dubliniensis and Candida albicans 总被引:1,自引:0,他引:1
Sullivan DJ Moran GP Pinjon E Al-Mosaid A Stokes C Vaughan C Coleman DC 《FEMS yeast research》2004,4(4-5):369-376
Candida dubliniensis is a pathogenic yeast species that was first identified as a distinct taxon in 1995. Epidemiological studies have shown that C. dubliniensis is prevalent throughout the world and that it is primarily associated with oral carriage and oropharyngeal infections in human immunodeficiency virus (HIV)-infected and acquired immune deficiency syndrome (AIDS) patients. However, unlike Candida albicans, C. dubliniensis is rarely found in the oral microflora of normal healthy individuals and is responsible for as few as 2% of cases of candidemia (compared to approximately 65% for C. albicans). The vast majority of C. dubliniensis isolates identified to date are susceptible to all of the commonly used antifungal agents, however, reduced susceptibility to azole drugs has been observed in clinical isolates and can be readily induced in vitro. The primary mechanism of fluconazole resistance in C. dubliniensis has been shown to be overexpression of the major facilitator efflux pump Mdr1p. It has also been observed that a large number of C. dubliniensis strains express a non-functional truncated form of Cdr1p, and it has been demonstrated that this protein does not play a significant role in fluconazole resistance in the majority of strains examined to date. Data from a limited number of infection models reflect findings from epidemiological studies and suggest that C. dubliniensis is less pathogenic than C. albicans. The reasons for the reduced virulence of C. dubliniensis are not clear as it has been shown that the two species express a similar range of virulence factors. However, although C. dubliniensis produces hyphae, it appears that the conditions and dynamics of induction may differ from those in C. albicans. In addition, C. dubliniensis is less tolerant of environmental stresses such as elevated temperature and NaCl and H(2)O(2) concentration, suggesting that C. albicans may have a competitive advantage when colonising and causing infection in the human body. It is our hypothesis that a genomic comparison between these two closely-related species will help to identify virulence factors responsible for the far greater virulence of C. albicans and possibly identify factors that are specifically implicated in either superficial or systemic candidal infections. 相似文献
100.
Pritchard KA Ou J Ou Z Shi Y Franciosi JP Signorino P Kaul S Ackland-Berglund C Witte K Holzhauer S Mohandas N Guice KS Oldham KT Hillery CA 《American journal of physiology. Lung cellular and molecular physiology》2004,286(4):L705-L714
Vaso-occlusive events are the major source of morbidity and mortality in sickle cell disease (SCD); however, the pathogenic mechanisms driving these events remain unclear. Using hypoxia to induce pulmonary injury, we investigated mechanisms by which sickle hemoglobin increases susceptibility to lung injury in a murine model of SCD, where mice either exclusively express the human alpha/sickle beta-globin (halphabetaS) transgene (SCD mice) or are heterozygous for the normal murine beta-globin gene and express the halphabetaS transgene (mbeta+/-, halphabetaS+/-; heterozygote SCD mice). Under normoxia, lungs from the SCD mice contained higher levels of xanthine oxidase (XO), nitrotyrosine, and cGMP than controls (C57BL/6 mice). Hypoxia increased XO and nitrotyrosine and decreased cGMP content in the lungs of all mice. After hypoxia, vascular congestion was increased in lungs with a greater content of XO and nitrotyrosine. Under normoxia, the association of heat shock protein 90 (HSP90) with endothelial nitric oxide synthase (eNOS) in lungs of SCD and heterozygote SCD mice was decreased compared with the levels of association in lungs of controls. Hypoxia further decreased association of HSP90 with eNOS in lungs of SCD and heterozygote SCD mice, but not in the control lungs. Pretreatment of rat pulmonary microvascular endothelial cells in vitro with xanthine/XO decreased A-23187-stimulated nitrite + nitrate production and HSP90 interactions with eNOS. These data support the hypotheses that hypoxia increases XO release from ischemic tissues and that the local increase in XO-induced oxidative stress can then inhibit HSP90 interactions with eNOS, decreasing *NO generation and predisposing the lung to vaso-occlusion. 相似文献