全文获取类型
收费全文 | 280篇 |
免费 | 24篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 2篇 |
2020年 | 4篇 |
2019年 | 1篇 |
2018年 | 5篇 |
2017年 | 3篇 |
2016年 | 6篇 |
2015年 | 8篇 |
2014年 | 8篇 |
2013年 | 17篇 |
2012年 | 20篇 |
2011年 | 22篇 |
2010年 | 13篇 |
2009年 | 15篇 |
2008年 | 14篇 |
2007年 | 12篇 |
2006年 | 13篇 |
2005年 | 18篇 |
2004年 | 16篇 |
2003年 | 12篇 |
2002年 | 15篇 |
2001年 | 2篇 |
2000年 | 6篇 |
1998年 | 5篇 |
1997年 | 1篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 3篇 |
1990年 | 5篇 |
1989年 | 1篇 |
1988年 | 4篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 3篇 |
1984年 | 4篇 |
1983年 | 5篇 |
1982年 | 3篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1975年 | 1篇 |
1974年 | 3篇 |
1973年 | 1篇 |
1972年 | 3篇 |
1968年 | 1篇 |
排序方式: 共有304条查询结果,搜索用时 78 毫秒
141.
142.
An increase in intermediate filaments has been reported in rat uterine stromal cells undergoing decidualization in vivo and in vitro. In order to identify biochemical correlates of this morphological change, we have identified (two dimensional gel electrophoresis, Western blots, indirect immunofluorescent staining) the constitutive intermediate filament proteins of stromal cells decidualizing in vivo and isolated stroma decidualizing in vitro as vimentin and desmin. Vimentin is common to all uterine stromal cells but increases, proportional to total cell protein, in decidualized stroma. Barely detectable in nondecidualized stroma, desmin, unlike vimentin, increases during decidualization at a rate greater than the increase in total cell protein. Neither the increase in vimentin or desmin is observed in hormonally sensitized, nondecidual stromal cells. Desmin, because it is selectively expressed in decidualizing stroma, could be considered unique enough to serve as a marker of decidual cell differentiation. 相似文献
143.
Flow dialysis measurements of calcium binding to bovine brain S100 alpha alpha, S100a (alpha beta), and S100b (beta beta) proteins in 20 mM Tris-HCl buffer at pH 7.5 and 8.3 revealed that S100 proteins bind specifically 4 Ca2+ eq/mol of protein dimer. The specific calcium-binding sites had, therefore, been assigned to typical amino acid sequences on the alpha and beta subunit. The protein affinity for calcium is much lower in the presence of magnesium and potassium. Potassium strongly antagonizes calcium binding on two calcium-binding sites responsible for most of the Ca2+-induced conformational changes on S100 proteins (probably site II alpha and site II beta). Zinc-binding studies in the absence of divalent cations revealed eight zinc-binding sites/mol of S100b protein dimer that we assumed to correspond to 4 zinc-binding sites/beta subunit. Zinc binding to S100b studied with UV spectroscopy methods showed that the occupation of the four higher affinity sites and the four lower affinity sites on the protein dimer were responsible for different conformational changes in S100b structure. Zinc binding on the higher affinity sites regulates calcium binding to S100b by increasing the protein affinity for calcium and decreasing the antagonistic effect of potassium on calcium binding. Zinc-binding studies on S100a and S100 alpha alpha protein showed that the Trp-containing S100 proteins bind zinc more weakly than S100b protein. Calcium-binding studies on zinc-bound S100a proved that calcium- and zinc-binding sites were distinct although there was no increase in zinc-bound S100a affinity for calcium, as in S100b protein. Finally we provide evidence that discrepancies between previously published results on the optical properties of S100b protein probably result from oxidation of the sulfhydryl groups in the protein. 相似文献
144.
In vitro interaction of premazepam with benzodiazepine receptors in rat brain regions 总被引:1,自引:0,他引:1
Premazepam (PRZ) in vitro competitively displaced 3H-diazepam (DIA), 3H-flunitrazepam (FLU) and 3H-RO 15-1788 from their binding sites on rat brain synaptosomes, with a potency intermediate to other benzodiazepines (BDZs), and Hill coefficients near 1 in different brain regions. Incubation at 37 degrees C reduced premazepam's affinity for BDZ receptors to a lower extent than other benzodiazepines and had no effect on the Hill coefficient. The IC50 of PRZ on 3H-RO 15-1788 and 3H-FLU binding was markedly reduced by GABA in rat cortex, like those of reference classical BDZs, but was GABA-independent in the cerebellum. The IC50 of the BDZ antagonist, RO 15-1788 was unaffected by GABA in both brain areas. The possibility that PRZ behaves as a partial agonist in the cortex and as an antagonist in the cerebellum is discussed. 相似文献
145.
Large-scale importation of bushmeat from West and Central Africa into Europe was reported in 2010. We sampled 18 illegal African bushmeat consignments seized at Charles de Gaulle airport, Paris, France and tested for the presence of bacteria. Additionally, five smuggled smoked fish were analysed for polycyclic aromatic hydrocarbons, which are known carcinogens. All bushmeat samples had viable counts of aerobic bacteria above levels considered safe for human consumption. We also identified zoonotic bacterial pathogens in bushmeat and unsafe levels of carcinogens in fish. The illegal importation of meat is a potential risk for the introduction of pathogens. 相似文献
146.
Nicholas Carlson Kristine Hommel Jonas Bjerring Olesen Anne-Merete Soja Tina Vilsb?ll Anne-Lise Kamper Christian Torp-Pedersen Gunnar Gislason 《PloS one》2016,11(2)
Introduction
Dialysis-requiring acute kidney injury is a severe illness associated with poor prognosis. However, information pertaining to incidence rates and prevalence of risk factors remains limited in spite of increasing focus. We evaluate time trends of incidence rates and changing patterns in prevalence of comorbidities, concurrent medication, and other risk factors in nationwide retrospective cohort study.Materials and Methods
All patients with dialysis-requiring acute kidney injury were identified between January 1st 2000 and December 31st 2012. By cross-referencing data from national administrative registries, the association of changing patterns in dialysis treatment, comorbidity, concurrent medication and demographics with incidence of dialysis-requiring acute kidney injury was evaluated.Results
A total of 18,561 adult patients with dialysis-requiring AKI were identified between 2000 and 2012. Crude incidence rate of dialysis-requiring AKI increased from 143 per million (95% confidence interval, 137–144) in 2000 to 366 per million (357–375) in 2006, and remained stable hereafter. Notably, incidence of continuous veno-venous hemodialysis (CRRT) and use of acute renal replacement therapy in elderly >75 years increased substantially from 23 per million (20–26) and 328 per million (300–355) in 2000, to 213 per million (206–220) and 1124 per million (1076–1172) in 2012, respectively. Simultaneously, patient characteristics and demographics shifted towards increased age and comorbidity.Conclusions
Although growth in crude incidence rate of dialysis-requiring AKI stabilized in 2006, continuous growth in use of CRRT, and acute renal replacement therapy of elderly patients >75 years, was observed. Our results indicate an underlying shift in clinical paradigm, as opposed to unadulterated growth in incidence of dialysis-requiring AKI. 相似文献147.
Megha Rajaram Jianping Zhang Tim Wang Jinyu Li Cem Kuscu Huan Qi Mamoru Kato Vladimir Grubor Robert J. Weil Aslaug Helland Anne-Lise Borrenson-Dale Kathleen R. Cho Douglas A. Levine Alan N. Houghton Jedd D. Wolchok Lois Myeroff Sanford D. Markowitz Scott W. Lowe Michael Zhang Alex Krasnitz Robert Lucito David Mu R. Scott Powers 《PloS one》2013,8(6)
One of the key questions about genomic alterations in cancer is whether they are functional in the sense of contributing to the selective advantage of tumor cells. The frequency with which an alteration occurs might reflect its ability to increase cancer cell growth, or alternatively, enhanced instability of a locus may increase the frequency with which it is found to be aberrant in tumors, regardless of oncogenic impact. Here we’ve addressed this on a genome-wide scale for cancer-associated focal deletions, which are known to pinpoint both tumor suppressor genes (tumor suppressors) and unstable loci. Based on DNA copy number analysis of over one-thousand human cancers representing ten different tumor types, we observed five loci with focal deletion frequencies above 5%, including the A2BP1 gene at 16p13.3 and the MACROD2 gene at 20p12.1. However, neither RNA expression nor functional studies support a tumor suppressor role for either gene. Further analyses suggest instead that these are sites of increased genomic instability and that they resemble common fragile sites (CFS). Genome-wide analysis revealed properties of CFS-like recurrent deletions that distinguish them from deletions affecting tumor suppressor genes, including their isolation at specific loci away from other genomic deletion sites, a considerably smaller deletion size, and dispersal throughout the affected locus rather than assembly at a common site of overlap. Additionally, CFS-like deletions have less impact on gene expression and are enriched in cell lines compared to primary tumors. We show that loci affected by CFS-like deletions are often distinct from known common fragile sites. Indeed, we find that each tumor tissue type has its own spectrum of CFS-like deletions, and that colon cancers have many more CFS-like deletions than other tumor types. We present simple rules that can pinpoint focal deletions that are not CFS-like and more likely to affect functional tumor suppressors. 相似文献
148.
149.
Thomas Fleischer Arnoldo Frigessi Kevin C Johnson Hege Edvardsen Nizar Touleimat Jovana Klajic Margit LH Riis Vilde D Haakensen Fredrik W?rnberg Bj?rn Naume ?slaug Helland Anne-Lise B?rresen-Dale J?rg Tost Brock C Christensen Vessela N Kristensen 《Genome biology》2014,15(8)