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   617篇
  免费   55篇
  国内免费   2篇
  674篇
  2023年   9篇
  2022年   26篇
  2021年   53篇
  2020年   35篇
  2019年   67篇
  2018年   53篇
  2017年   23篇
  2016年   34篇
  2015年   30篇
  2014年   34篇
  2013年   42篇
  2012年   32篇
  2011年   44篇
  2010年   19篇
  2009年   19篇
  2008年   21篇
  2007年   27篇
  2006年   13篇
  2005年   16篇
  2004年   15篇
  2003年   3篇
  2002年   8篇
  2001年   3篇
  1999年   1篇
  1998年   2篇
  1997年   2篇
  1996年   1篇
  1995年   1篇
  1994年   1篇
  1993年   3篇
  1992年   1篇
  1991年   1篇
  1989年   5篇
  1988年   2篇
  1987年   3篇
  1986年   5篇
  1985年   2篇
  1984年   3篇
  1983年   1篇
  1982年   1篇
  1979年   2篇
  1978年   1篇
  1977年   1篇
  1975年   1篇
  1971年   1篇
  1970年   2篇
  1967年   1篇
  1965年   1篇
  1962年   1篇
  1960年   1篇
排序方式: 共有674条查询结果,搜索用时 15 毫秒
81.
The adult glial progenitor cells were recently shown to be able to produce neurons in central nervous system (CNS) and to become multipotent in vitro. Although the fate decision of glial progenitors was studied extensively, the signals and factors which regulate the timing of neuronal differentiation still remain unknown. To elucidate the mechanisms underlying the neuronal differentiation from glial progenitors, we modified the gene expression profile in NG2+ glial progenitor cells using enhanced retroviral mutagen (ERM) technique followed by phenotype screening to identify possible gene(s) responsible for glial-neuronal cell fate determination. Among the identified molecules, we found the gene named non-metastatic cell 1 which encodes a nucleoside diphosphate kinase protein A (Nm23-M1 or NME1). So far, the Nm23 members have been shown to be involved in various molecular processes including tumor metastasis, cell proliferation, differentiation and cell fate determination. In the present study, we provide evidence suggesting the role of NME1 in glial-neuronal cell fate determination in vitro. We showed that NME1 is widely expressed in neuronal structures throughout adult mouse CNS. Our immunohistochemical results revealed that NME1 is strongly colocalized with NF200 through white matter of spinal cord and brain. Interestingly, NME1 overexpression in oligodendrocyte progenitor OLN-93 cells potently induced the acquisition of neuronal fate, while its silencing was shown to promote oligodendrocyte differentiation. Furthermore, we demonstrated that dual-functional role of NME1 is achieved through cAMP-dependent protein kinase (PKA). Our data therefore suggested that NME1 acts as a switcher or reprogramming factor which involves in oligodentrocyte versus neuron cell fate specification in vitro.  相似文献   
82.

Background

Identifying patients with diabetes at increased risk of chronic kidney disease (CKD) is essential to prevent/slow the progression to end-stage renal disease (ESRD). CKD and diabetic peripheral neuropathy (DPN) share common mechanisms. Hence, we aimed to examine the relationship between foot insensitivity and CKD in patients with Type 2 diabetes.

Methods

A prospective observational cohort study in adults with Type 2 diabetes. Patients with ESRD were excluded. Foot insensitivity was assessed using the 10-g monofilament test. Renal function was assessed using estimated glomerular filtration rate (eGFR) based on the MDRD equation. Albuminuria was defined as the presence of urinary albumin/creatinine ratio (ACR) >3.4 mg/mmol.

Results

Two hundred and twenty eight patients were recruited and followed-up for 2.5 years. One hundred and ninety patients (83.4%) had eGFR?≥?60 ml/min/1.73 m2. Seventy six (33.3%) patients had foot insensitivity (i.e. abnormal monofilament test). Patients with foot insensitivity had lower eGFR and higher prevalence of albuminuria compared to patients with normal monofilament test. After adjustment for age, gender, ethnicity, diabetes duration, HbA1c, body mass index, insulin treatment, number of anti-hypertensives, history of peripheral vascular disease, and baseline eGFR (R2 0.87), baseline foot insensitivity was associated with study-end eGFR (B?=??3.551, p?=?0.036).

Conclusions

Patients with Type 2 diabetes and foot insensitivity are at increased risk of eGFR decline. Identifying these patients offers an opportunity to intensify metabolic and blood pressure control to prevent/retard the development of CKD. Future studies of larger sample size and longer follow up from multiple centres are needed to assess the diagnostic performance of our findings in predicting CKD development, and to compare the performance of the monofilament test with albuminuria.
  相似文献   
83.
Experimental and Applied Acarology - This study examined the acaricidal, histopathological and genotoxic effects of the entomopathogenic fungus Beauveria bassiana on engorged females of the fowl...  相似文献   
84.
Numerous investigators have provided data supporting essential roles for insulin-like growth factor-I (IGF-I) in development of the brain. The aim of this study was to immunohistochemically determine the distinct regional distribution pattern of IGF-1 receptor (IGF-IR) expression in various portions of newborn rat hippocampus on postnatal days 0 (P0), 7 (P7), and 14 (P14), with comparison between male/female and right/left hippocampi. We found an overall significant increase in distribution of IGF-IR-positive (IGF-IR+) cells in CA1 from P0 until P14. Although, no marked changes in distribution of IGF-IR+ cells in areas CA2 and CA3 were observed; IGF-IR+ cells in DG decreased until P14. The smallest number of immunoreactive cells was present in CA2 and the highest number in DG at P0. Moreover, in CA1, CA3, and DG, the number of IGF-IR+ cells was markedly higher in both sides of the hippocampus in females. Our data also showed a higher mean number of IGF-IR+ cells in the left hippocampus of female at P7. By contrast, male pups showed a significantly higher number of IGF-IR+ cells in the DG of the right hippocampus. At P14, the mean number of immunoreactive cells in CA1, CA3, and DG areas found to be significantly increased in left side of hippocampus of males, compared to females. These results indicate the existence of a differential distribution pattern of IGF-IR between left–right and male–female hippocampi. Together with other mechanisms, these differences may underlie sexual dimorphism and left–right asymmetry in the hippocampus.  相似文献   
85.
International Microbiology - In the present work, the extensive biological activities of marine endophytic Streptomyces strains isolated from marine soft coral Sarcophyton convolutum have been...  相似文献   
86.
Spore suspensions of Aspergillus oryzae NRRL 3484 were subjected to mutagenesis using ultraviolet-irradiation followed by chemical treatments to improve the biosynthesis of cellulase. Ten mutant strains namely UEAC7, UEAR5, UNAC4, UNAC16, UNAR19, UNBC7, UNBR3, UNBR10, UNBR23 and UNBR25 were selected and their extracellular cellulase activities were assayed. Mutant UNAC4 gave the highest cellulase production [2,455 ± 28 U/g-dry substrate (ds) for filter paper-ase (FP-ase)] in a yield 4-fold exceeding that of the wild type strain (578 ± 5.0 U/g-ds for FP-ase). Rice straw (RS) was used as a sole carbon source for the enzyme production at a concentration of 10 % (w/v). Maximum cellulase production was achieved at initial medium pH 5.5, initial moisture content 77 % and an incubation temperature 28 °C on the fifth day of growth. NH4Cl proved to be the suitable added nitrogen source for maximum enzyme production followed by peptone. These results clearly indicate the cost-effectiveness of solid state fermentation technology in the economic production of extracellular cellulase. The hyper-production of cellulase by mutant strain UNAC4 has potential for industrial processes that convert lignocellulosic material (e.g. RS) into products of commercial value such as glucose and biofuels.  相似文献   
87.
In the present study, we compared the response to salinity of three plants from Brittany coast with contrasted ecological status: Limonium latifolium (salt marshes), Matricaria maritima (beach tops and sand dunes) and Crambe maritima (fixed dunes). Under controlled glasshouse conditions, the growth of the three plants decreased with increasing external salinity. L. latifolium and C. maritima exhibited the highest and lowest resistance to severe salt stress (400 mM), respectively. M. maritima could be considered as an intermediate species, since it tolerated salinity up to 200 mM. The same observation could be made with sodium absorption and acuumulation in plant tissues, the most tolerant species (L. latifolium being the least Na accumulator. Hydrogen peroxide (H2O2) and malondialdehyde (MDA), commonly produced in conditions of stress, accumulated significantly in salt treated C. maritima and M. maritima while not in the tolerant L. latifolium. The latter used glutathione reductase to maintain constant H2O2 levels under salt stress while peroxidases were very low and ascorbate peroxidase did not respond to salinity stimulation. The medium tolerant halophyte M. maritima used peroxidases to protect from NaCl-induced H2O2, while the sensitive C. maritima failed to detoxify H2O2 despite a sharp increase in catalase activity. Results showed that the three coastal species differ in resistance to salinity. They also suggested that the level of plant resistance to salinity could be attributed to differing mechanisms to manage the accumulation of sodium and cope with the oxidative damages.  相似文献   
88.
The ionome is the elemental composition of a living organism, its tissues, cells or cell compartments. The ionomes of roots, stems and leaves of 14 native Brazilian forest species were characterised to examine the relationships between plant and organ ionomes and the phylogenetic and ecological affiliations of species. The null hypothesis that ionomes of Brazilian forest species and their organs do not differ was tested. Concentrations of mineral nutrients in roots, stems and leaves were determined for 14 Brazilian forest species, representing seven angiosperm orders, grown hydroponically in a complete nutrient solution. The 14 species could be differentiated by their ionomes and the partitioning of mineral nutrients between organs. The ionomic differences between the 14 species did not reflect their phylogenetic relationships or successional ecology. Differences between shoot ionomes and root ionomes were greater than differences in the ionome of an organ when compared among genotypes. In conclusion, differences in ionomes of species and their organs reflect a combination of ancient phylogenetic and recent environmental adaptations.  相似文献   
89.
The effects of acute pretreatment of rats with corticosterone (5 and 20 mg/kg, s.c.) on emotional behavior, expression of c-Fos protein in brain structures, and serum concentration of corticosterone were studied to model the short-term glucocorticoid-dependent changes in brain functions. Corticosterone was administered 90 min before training of a conditioned fear reaction (a freezing response), and behavioral, hormonal and immunocytochemical effects were examined 1 day later, on the test day. Pretreatment of rats with corticosterone significantly attenuated the freezing reaction in the conditioned fear test. The effect of the corticosterone was accompanied by a selective enhancement of the aversive context-induced c-Fos expression in some brain structures: the parvocellular and magnocellular neurons of the paraventricular hypothalamic nucleus (pPVN and mPVN), the medial amygdala nucleus (MeA), and the cingulate cortex, area 1 (Cg1), as well as an increase in the concentration of aversive context-induced endogenous serum glucocorticoid, 1.5 h and 10 min after the test session, respectively. It is suggested that the behavioral effects of acute pretreatment of rats with corticosterone could be due to changes in the mnemonic processes in the brain, inhibition of brain corticotropin releasing factor (CRF) synthesis, or stimulation of GABA-A receptor modulating neurosteroids synthesis. It is hypothesized that the enhanced activity of Cg1, MeA, pPVN, and mPVN, and the hypothalamic-pituitary-adrenal axis with concomitant increased serum glucocorticoid concentration, might serve to facilitate active coping behavior in a threatening situation.  相似文献   
90.
Probiotics and Antimicrobial Proteins - This study was conducted to evaluate different doses of two species of Bacillus (Bacillus licheniformis and Bacillus subtilis), on growth parameters,...  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