首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   1113篇
  免费   63篇
  2022年   5篇
  2021年   20篇
  2020年   14篇
  2019年   16篇
  2018年   27篇
  2017年   15篇
  2016年   34篇
  2015年   46篇
  2014年   51篇
  2013年   67篇
  2012年   103篇
  2011年   78篇
  2010年   49篇
  2009年   46篇
  2008年   68篇
  2007年   51篇
  2006年   69篇
  2005年   42篇
  2004年   39篇
  2003年   27篇
  2002年   41篇
  2001年   21篇
  2000年   12篇
  1999年   10篇
  1998年   5篇
  1997年   5篇
  1995年   12篇
  1994年   4篇
  1993年   6篇
  1992年   4篇
  1991年   5篇
  1990年   4篇
  1989年   4篇
  1988年   7篇
  1987年   7篇
  1986年   7篇
  1985年   4篇
  1983年   4篇
  1982年   9篇
  1981年   4篇
  1965年   3篇
  1958年   3篇
  1956年   3篇
  1936年   3篇
  1929年   4篇
  1928年   6篇
  1919年   6篇
  1918年   3篇
  1913年   3篇
  1851年   10篇
排序方式: 共有1176条查询结果,搜索用时 31 毫秒
31.
Several strains of terrestrial algae isolated from biological soil crusts in Germany and Ukraine were identified by morphological methods as the widely distributed species Dictyosphaerium minutum (=Dictyosphaerium chlorelloides). Investigation of the phylogeny showed their position unexpectedly outside of Chlorellaceae (Trebouxiophyceae) and distantly from Chlorella chlorelloides, to which this taxon was attributed after revision of the genus Chlorella based on an integrative approach. SSU rRNA phylogeny determined the position of our strains inside a clade recently described as a new genus of the cryptic alga Xerochlorella olmiae isolated from desert biological soil crusts in the United States. Investigation of the morphology of the authentic strain of X. olmiae showed Dictyosphaerium-like morphology, as well as some other characters, common for our strains and morphospecies D. minutum. The latter alga was described as terrestrial and subsequently united with the earlier described aquatic representative D. chlorelloides because of their similar morphology. The revision of Chlorella mentioned above provided only one aquatic strain (D. chlorelloides), which determined its position in the genus. But terrestrial strains of the morphospecies were not investigated phylogenetically. Our study showed that the terrestrial D. minutum is not related to the morphologically similar D. chlorelloides (=Chlorella chlorelloides, Chlorellaceae), and instead represented a separate lineage in the Trebouxiophyceae, recently described as genus Xerochlorella. Therefore, revision of Xerochlorella is proposed, including nomenclatural combinations, epitypifications, and emendations of two species: X. minuta and X. dichotoma. New characters of the genus based on investigation of morphology and ultrastructure were determined.  相似文献   
32.
Molecular Biology Reports - Serotoninergic system is one of the most important neurotransmission systems investigated in the field of psychiatry. Extensive evidence reveals how alterations of this...  相似文献   
33.
34.
The use of mushroom extracts has been common practice in traditional medicine for centuries, including the treatment of cancer. Proteins called hydrophobins are very abundant in mushrooms. Here, it was examined whether they have antitumor activity. Hydrophobin SC3 of Schizophyllum commune was injected daily intraperitoneally starting 1 day after tumor induction in two tumor mouse models (sarcoma and melanoma). SC3 reduced the size and weight of the melanoma significantly, but the sarcoma seemed not affected. However, microscopic analysis of the tumors 12 days after induction revealed a strong antitumor effect of SC3 on both tumors. The mitotic activity of the tumor decreased 1.6- (melanoma) to 2.3-fold (sarcoma), while the vital mass decreased 2.3- (melanoma) to 4.3-fold (sarcoma) compared to the control. Treatment did not cause any signs of toxicity. Behavior, animal growth, and weight of organs were similar to animals injected with vehicle, and no histological abnormalities were found in the organs. In vitro cell culture studies revealed no direct cytotoxic effect of SC3 towards sarcoma cells, while cytotoxic activity was observed towards melanoma cells at a high SC3 concentration. Daily treatment with SC3 did not result in detectable levels of anti-SC3 antibodies in the plasma. Instead, a cellular immune response was observed. Incubation of spleen cells with SC3 resulted in a 1.5- to 2.5-fold increase in interleukin-10 and TNF-α mRNA levels. In conclusion, the nontoxic fungal hydrophobin SC3 showed tumor-suppressive activity possibly via immunomodulation and may be of benefit as adjuvant in combination with chemotherapy and radiation.  相似文献   
35.
36.
The vegetative growth of Ulva lactuca was studied to determine if the growth rate of the alga is driven by infradian rhythmicity. The influence of temperature on the infradian rhythm of growth was also investigated. Discs of Ulva were grown in controlled laboratory conditions at different combinations of temperature (5, 10, 15, 20°С) and irradiance (40 and 60 μmol photons m?2 s?1) under 12 : 12 h light : dark cycles. The growth rates exhibited a rhythmic pattern with one major peak every 2 or 3 days. Growth at 5 or 10°С increased the prevalence of 3-day cycles and maintained U. lactuca in the vegetative growth stage. In contrast, growth at 15 or 20°С provoked a predominance of the 2-day cycle and induced reproduction. The 2- or 3-day cycles were combined in longer cycles having a period close to 6 days. We suppose that the 2-, 3- and 6-day rhythms of physiological processes are related to large-scale Rossby and Kelvin waves, which produce oscillations in the geomagnetic field and seawater temperature with the same periods. The predominance of 2-day or 3-day fluctuations of the geomagnetic field and temperature probably determine the prevalence of reproduction and vegetative growth, respectively, in Ulva.  相似文献   
37.
记述采自广西大明山自然保护区的天牛科2中国新记录种:斯维颠花天牛Saligranta svihlai(Holzschuh,1989)和少瘤星天牛Anoplophora granata Holzschuh,1993。  相似文献   
38.

Background

Retinal dystrophies (RD) are a group of hereditary diseases that lead to debilitating visual impairment and are usually transmitted as a Mendelian trait. Pathogenic mutations can occur in any of the 100 or more disease genes identified so far, making molecular diagnosis a rather laborious process. In this work we explored the use of whole exome sequencing (WES) as a tool for identification of RD mutations, with the aim of assessing its applicability in a diagnostic context.

Methodology/Principal Findings

We ascertained 12 Spanish families with seemingly recessive RD. All of the index patients underwent mutational pre-screening by chip-based sequence hybridization and resulted to be negative for known RD mutations. With the exception of one pedigree, to simulate a standard diagnostic scenario we processed by WES only the DNA from the index patient of each family, followed by in silico data analysis. We successfully identified causative mutations in patients from 10 different families, which were later verified by Sanger sequencing and co-segregation analyses. Specifically, we detected pathogenic DNA variants (∼50% novel mutations) in the genes RP1, USH2A, CNGB3, NMNAT1, CHM, and ABCA4, responsible for retinitis pigmentosa, Usher syndrome, achromatopsia, Leber congenital amaurosis, choroideremia, or recessive Stargardt/cone-rod dystrophy cases.

Conclusions/Significance

Despite the absence of genetic information from other family members that could help excluding nonpathogenic DNA variants, we could detect causative mutations in a variety of genes known to represent a wide spectrum of clinical phenotypes in 83% of the patients analyzed. Considering the constant drop in costs for human exome sequencing and the relative simplicity of the analyses made, this technique could represent a valuable tool for molecular diagnostics or genetic research, even in cases for which no genotypes from family members are available.  相似文献   
39.
Mortality from bacterial meningitis in African adults is significantly higher than those in better resourced settings and adjunctive therapeutic interventions such as dexamethasone and glycerol have been shown to be ineffective. We conducted a study analysing data from clinical trials of bacterial meningitis in Blantyre, Malawi to investigate the clinical parameters associated with this high mortality.

Methods

We searched for all clinical trials undertaken in Blantyre investigating bacterial meningitis from 1990 to the current time and combined the data from all included trial datasets into one database. We used logistic regression to relate individual clinical parameters to mortality. Adults with community acquired bacterial meningitis were included if the CSF culture isolate was consistent with meningitis or if the CSF white cell count was >100 cells/mm3 (>50% neutrophils) in HIV negative participants and >5 cells/mm3 in HIV positive participants. Outcome was measured by mortality at discharge from hospital (after 10 days of antibiotic therapy) and community follow up (day 40).

Results

Seven hundred and fifteen episodes of bacterial meningitis were evaluated. The mortality rate was 45% at day 10 and 54% at day 40. The most common pathogens were S.pneumoniae (84% of positive CSF isolates) and N.meningitidis (4%). 607/694 (87%) participants tested were HIV antibody positive. Treatment delays within the hospital system were marked. The median presenting GCS was 12/15, 17% had GCS<8 and 44.9% had a seizure during the illness. Coma, seizures, tachycardia and anaemia were all significantly associated with mortality on multivariate analysis. HIV status and pneumococcal culture positivity in the CSF were not associated with mortality. Adults with community acquired bacterial meningitis in Malawi present with a severe clinical phenotype. Predictors of high mortality are different to those seen in Western settings. Optimising in-hospital care and minimising treatment delays presents an opportunity to improve outcomes considerably.  相似文献   
40.
BackgroundIn vitro diagnostic (IVD) investigations are indispensable for routine patient management. Appropriate testing allows early-stage interventions, reducing late-stage healthcare expenditure (HCE).AimTo investigate HCE on IVDs in two developed markets and to assess the perceived value of IVDs on clinical decision-making. Physician-perceived HCE on IVD was evaluated, as well as desired features of new diagnostic markers.MethodsPast and current HCE on IVD was calculated for the US and Germany. A total of 79 US/German oncologists and cardiologists were interviewed to assess the number of cases where: physicians ask for IVDs; IVDs are used for initial diagnosis, treatment monitoring, or post-treatment; and decision-making is based on an IVD test result. A sample of 201 US and German oncologists and cardiologists was questioned regarding the proportion of HCE they believed to be attributable to IVD testing. After disclosing the actual IVD HCE, the physician’s perception of the appropriateness of the amount was captured. Finally, the association between physician-rated impact of IVD on decision-making and perceived contribution of IVD expenditure on overall HCE was assessed.ResultsIVD costs account for 2.3% and 1.4% of total HCE in the US and Germany. Most physicians (81%) believed that the actual HCE on IVDs was >5%; 19% rated the spending correctly (0–4%, p<0.001). When informed of the actual amount, 64% of physicians rated this as appropriate (p<0.0001); 66% of decision-making was based on IVD. Significantly, more physicians asked for either additional clinical or combined clinical/health economic data than for the product (test/platform) alone (p<0.0001).ConclusionsOur results indicate a poor awareness of actual HCE on IVD, but a high attributable value of diagnostic procedures for patient management. New markers should deliver actionable and medically relevant information, to guide decision-making and foster improved patient outcomes.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号