全文获取类型
收费全文 | 573篇 |
免费 | 49篇 |
国内免费 | 2篇 |
出版年
2022年 | 10篇 |
2021年 | 21篇 |
2020年 | 7篇 |
2019年 | 9篇 |
2018年 | 14篇 |
2017年 | 8篇 |
2016年 | 10篇 |
2015年 | 20篇 |
2014年 | 24篇 |
2013年 | 31篇 |
2012年 | 35篇 |
2011年 | 50篇 |
2010年 | 15篇 |
2009年 | 15篇 |
2008年 | 22篇 |
2007年 | 28篇 |
2006年 | 24篇 |
2005年 | 34篇 |
2004年 | 17篇 |
2003年 | 29篇 |
2002年 | 21篇 |
2001年 | 11篇 |
2000年 | 8篇 |
1999年 | 9篇 |
1998年 | 5篇 |
1996年 | 7篇 |
1994年 | 3篇 |
1992年 | 5篇 |
1990年 | 5篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1984年 | 6篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1980年 | 6篇 |
1979年 | 9篇 |
1978年 | 5篇 |
1977年 | 3篇 |
1975年 | 5篇 |
1974年 | 4篇 |
1972年 | 4篇 |
1967年 | 4篇 |
1961年 | 3篇 |
1941年 | 3篇 |
1931年 | 3篇 |
1930年 | 2篇 |
1929年 | 2篇 |
1927年 | 3篇 |
排序方式: 共有624条查询结果,搜索用时 15 毫秒
41.
Antczak C Shum D Escobar S Bassit B Kim E Seshan VE Wu N Yang G Ouerfelli O Li YM Scheinberg DA Djaballah H 《Journal of biomolecular screening》2007,12(4):521-535
The human mitochondrial peptide deformylase (HsPDF) provides a potential new target for broadly acting antiproliferative agents. To identify novel nonpeptidomimetic and nonhydroxamic acid-based inhibitors of HsPDF, the authors have developed a high-throughput screening (HTS) strategy using a fluorescence polarization (FP)-based binding assay as the primary assay for screening chemical libraries, followed by an enzymatic-based assay to confirm hits, prior to characterization of their antiproliferative activity against established tumor cell lines. The authors present the results and performance of the established strategy tested in a pilot screen of 2880 compounds and the identification of the 1st inhibitors. Two common scaffolds were identified within the hits. Furthermore, cytotoxicity studies revealed that most of the confirmed hits have antiproliferative activity. These findings demonstrate that the designed strategy can identify novel functional inhibitors and provide a powerful alternative to the use of functional assays in HTS and support the hypothesis that HsPDF inhibitors may constitute a new class of antiproliferative agent. 相似文献
42.
Wang CC Chu KO Chong WS Li WY Pang CP Shum AS Lau TK Rogers MS 《Free radical biology & medicine》2007,43(4):519-527
Tea is the most common beverage after water. Concerns have been raised about the safety of tea during pregnancy, especially for embryo development. We aimed at studying the effects of active tea components on developing embryos by in vitro rat embryo culture. Rat embryos during early organogenesis were cultivated in serum supplemented with one of the tea catechins. Developmental hallmarks and malformations (Mal) in the developing embryos were compared and evaluated by a standard morphological scoring system. The embryotoxicity of each tea catechin was classified according to the European Center for the Validation of Alternative Methods. Cell viability was assessed by supervital dye staining, apoptosis by TUNEL assay, and peroxidation by the 8-isoprostane EIA method. We found that (+)-catechin had the least effect on developing embryos (Mal(50)=715.1 mg/L; IC50(Mal)=435 mg/L), whereas (-)-epigallocatechin gallate had the most adverse effect (Mal(50)=54.2 mg/L; IC50(Mal)=45.8 mg/L). The major malformation in affected embryos included caudal retardation with abnormal axial flexion and delayed hind-limb formation. All catechins were classified as nonembryotoxic except (-)-epigallocatechin gallate, which was classified as weakly embryotoxic. With (-)-epigallocatechin gallate, increased numbers of nonviable and apoptotic cells in the malformed embryos were associated with increased embryo 8-isoprostane. 相似文献
43.
Ramajayam R Giridhar R Yadav MR Djaballah H Shum D Radu C 《Journal of enzyme inhibition and medicinal chemistry》2007,22(6):716-721
Novel substituted 5,7-diaryl-2,3-dihydro-1,4-diazepines and 4,6-diaryl-2-aminopyrimidines were synthesized and tested for their antiproliferative activity. Title compounds were obtained by cyclocondensation of a substituted flavone with ethylenediamine and guanidine respectively. The cytotoxicity in vitro against various human leukemic cancer cell lines viz., Jurkat, HL60, MOLT3, NCEB-1, K562 was determined. 相似文献
44.
There is growing evidence that molecular testing is feasible on all types of cytological preparation, which is fortunate as more diagnostic markers and biomarkers for targeted therapies are discovered for use in pulmonary and pleural malignancies. In this article we will discuss the pre-analytic, analytic, and post-analytic (interpretive) considerations for successful implementation of molecular tests for diagnostic and predictive markers in respiratory and pleural cytology. The vast majority of laboratories are familiar with, and have validated their molecular protocols for, formalin-fixed paraffin-embedded surgical specimens, which are not directly applicable to cytology specimens. Thus, rigorous validation must be performed for each type of fixative and cytology preparation before it is implemented in the clinical setting. 相似文献
45.
46.
47.
48.
Paik J Fierce Y Mai PO Phelps SR McDonald T Treuting P Drivdahl R Brabb T LeBoeuf R O'Brien KD Maggio-Price L 《Comparative medicine》2011,61(4):330-338
Murine norovirus (MNV) is prevalent in rodent facilities in the United States. Because MNV has a tropism for macrophages and dendritic cells, we hypothesized that it may alter phenotypes of murine models of inflammatory diseases, such as obesity and atherosclerosis. We examined whether MNV infection influences phenotypes associated with diet-induced obesity and atherosclerosis by using Ldlr(-/-) mice. Male Ldlr(-/-) mice were maintained on either a diabetogenic or high-fat diet for 16 wk, inoculated with either MNV or vehicle, and monitored for changes in body weight, blood glucose, glucose tolerance, and insulin sensitivity. Influence of MNV on atherosclerosis was analyzed by determining aortic sinus lesion area. Under both dietary regimens, MNV-infected and control mice gained similar amounts of weight and developed similar degrees of insulin resistance. However, MNV infection was associated with significant increases in aortic sinus lesion area and macrophage content in Ldlr(-/-) mice fed a high-fat diet but not those fed a diabetogenic diet. In conclusion, MNV infection exacerbates atherosclerosis in Ldlr(-/-) mice fed a high-fat diet but does not influence obesity- and diabetes-related phenotypes. Increased lesion size was associated with increased macrophages, suggesting that MNV may influence macrophage activation or accumulation in the lesion area. 相似文献
49.
Kasperavičiūtė D Catarino CB Chinthapalli K Clayton LM Thom M Martinian L Cohen H Adalat S Bockenhauer D Pope SA Lench N Koltzenburg M Duncan JS Hammond P Hennekam RC Land JM Sisodiya SM 《PloS one》2011,6(8):e23182
Background
Patients with epilepsy often suffer from other important conditions. The existence of such co-morbidities is frequently not recognized and their relationship with epilepsy usually remains unexplained.Methodology/Principal Findings
We describe three patients with common, sporadic, non-syndromic epilepsies in whom large genomic microdeletions were found during a study of genetic susceptibility to epilepsy. We performed detailed gene-driven clinical investigations in each patient. Disruption of the function of genes in the deleted regions can explain co-morbidities in these patients.Conclusions/Significance
Co-morbidities in patients with epilepsy can be part of a genomic abnormality even in the absence of (known) congenital malformations or intellectual disabilities. Gene-driven phenotype examination can also reveal clinically significant unsuspected condition. 相似文献50.
Kawaguchi S Kurihara H King R Hale L Berli T Robinson JP Ishida A Wakita M Virtue P Nicol S Ishimatsu A 《Biology letters》2011,7(2):288-291
Antarctic krill embryos and larvae were experimentally exposed to 380 (control), 1000 and 2000 µatm pCO2 in order to assess the possible impact of ocean acidification on early development of krill. No significant effects were detected on embryonic development or larval behaviour at 1000 µatm pCO2; however, at 2000 µatm pCO2 development was disrupted before gastrulation in 90 per cent of embryos, and no larvae hatched successfully. Our model projections demonstrated that Southern Ocean sea water pCO2 could rise up to 1400 µatm in krill''s depth range under the IPCC IS92a scenario by the year 2100 (atmospheric pCO2 788 µatm). These results point out the urgent need for understanding the pCO2-response relationship for krill developmental and later stages, in order to predict the possible fate of this key species in the Southern Ocean. 相似文献