全文获取类型
收费全文 | 303篇 |
免费 | 17篇 |
专业分类
320篇 |
出版年
2022年 | 2篇 |
2021年 | 2篇 |
2020年 | 2篇 |
2019年 | 7篇 |
2018年 | 6篇 |
2017年 | 3篇 |
2016年 | 8篇 |
2015年 | 8篇 |
2014年 | 17篇 |
2013年 | 17篇 |
2012年 | 18篇 |
2011年 | 19篇 |
2010年 | 13篇 |
2009年 | 16篇 |
2008年 | 19篇 |
2007年 | 21篇 |
2006年 | 11篇 |
2005年 | 17篇 |
2004年 | 18篇 |
2003年 | 6篇 |
2002年 | 13篇 |
2001年 | 6篇 |
2000年 | 6篇 |
1999年 | 8篇 |
1998年 | 5篇 |
1997年 | 1篇 |
1996年 | 5篇 |
1995年 | 2篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 4篇 |
1990年 | 2篇 |
1988年 | 1篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 4篇 |
1983年 | 7篇 |
1982年 | 1篇 |
1981年 | 7篇 |
1978年 | 1篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1969年 | 1篇 |
1954年 | 2篇 |
排序方式: 共有320条查询结果,搜索用时 15 毫秒
101.
Oksana Shynlova Tamara Nedd‐Roderique Yunqing Li Anna Dorogin Tina Nguyen Stephen J. Lye 《Journal of cellular and molecular medicine》2013,17(2):311-324
Leucocyte infiltration in the decidua (maternal–foetal interface) before, during and after term (TL) and preterm labour (PTL) was studied in mouse. We also investigated the mechanism of peripheral leucocyte recruitment into decidua by analysing the tissue cytokine profiles. Decidual tissues were collected during late gestation, TL and post‐partum (PP). PTL was initiated on gestational day 15 by intrauterine injection of Lipopolysaccharide (LPS, 125 μg) or progesterone signalling antagonism by RU486. Animals were killed during PTL or PP. Decidua basalis was analysed using FACS and immunohistochemistry. Markers of myeloid cell differentiation (Gr1, Ly6G, Neu7/4, F4/80) were assessed to define tissue monocytes (M), neutrophils (N) and macrophages (Macs). Flow cytometry revealed a significant (P < 0.05) increase in decidual Macs prior to TL; M and N numbers increased during TL and further increased during PP, which correlated with immunohistochemistry data. Massive influx of N, but not Macs and M, was detected by FACS during LPS‐PTL (P < 0.05) but not RU486‐PTL. Highest levels of N infiltration into the decidua occurred PP in both LPS and RU486 groups. Decidual infiltration during TL and RU486‐PTL was accompanied by an increase in pro‐inflammatory cytokines (IL1b and IL6) and CCL2 chemokine; LPS‐PTL showed increases in multiple cytokines. PP period following TL and PTL was associated with further up‐regulation of multiple cytokines/chemokines (P < 0.05). Our data suggest a programme of myeloid cells involvement in parturition with the pre‐partum influx of Macs into the decidua contributing to the progression of labour, whereas the later influx of M and N contribute to PP decidual involution. 相似文献
102.
Duijnisveld BJ Bigot A Beenakker KG Portilho DM Raz V van der Heide HJ Visser CP Chaouch S Mamchaoui K Westendorp RG Mouly V Butler-Browne GS Nelissen RG Maier AB 《Arthritis research & therapy》2011,13(6):R207-10
Introduction
Chronic inflammation is a profound systemic modification of the cellular microenvironment which could affect survival, repair and maintenance of muscle stem cells. The aim of this study was to define the role of chronic inflammation on the regenerative potential of satellite cells in human muscle.Methods
As a model for chronic inflammation, 11 patients suffering from rheumatoid arthritis (RA) were included together with 16 patients with osteoarthritis (OA) as controls. The mean age of both groups was 64 years, with more females in the RA group compared to the OA group. During elective knee replacement surgery, a muscle biopsy was taken from the distal musculus vastus medialis. Cell populations from four RA and eight OA patients were used for extensive phenotyping because these cell populations showed no spontaneous differentiation and myogenic purity greater than 75% after explantation.Results
After mononuclear cell explantation, myogenic purity, viability, proliferation index, number of colonies, myogenic colonies, growth speed, maximum number of population doublings and fusion index were not different between RA and OA patients. Furthermore, the expression of proteins involved in replicative and stress-induced premature senescence and apoptosis, including p16, p21, p53, hTERT and cleaved caspase-3, was not different between RA and OA patients. Mean telomere length was shorter in the RA group compared to the OA group.Conclusions
In the present study we found evidence that chronic inflammation in RA does not affect the in vitro regenerative potential of human satellite cells. Identification of mechanisms influencing muscle regeneration by modulation of its microenvironment may, therefore, be more appropriate. 相似文献103.
The future application of human embryonic stem cells (hESC) for therapeutic approaches requires the development of xeno-free culture conditions to prevent the potential transmission of animal pathogens or xenobiotic substances to hESC. An important component of the majority of hESC culture systems developed is the requirement for fibroblasts to serve as feeders. For this purpose, several studies have used human foreskin fibroblasts established under xeno-free conditions. In this study we report xeno-free establishment and maintenance of human embryonic fibroblasts (XHEF) and demonstrate their ability to support long-term self-renewal of hESC under xeno-free culture conditions, using a commercially available complete medium. Importantly, our culture conditions allow enzymatic passaging of hESC. In contrast, hESC cultured on human foreskin fibroblasts (XHFF) under the same conditions were poorly maintained and rapidly subject to differentiation. Our study clearly shows that the source of human fibroblasts is essential for long-term xeno-free hESC maintenance. 相似文献
104.
105.
Say-Hean Lye Jagdish Kaur Chahil Pramod Bagali Livy Alex Jamunarani Vadivelu Wan Azman Wan Ahmad Siew-Pheng Chan Meow-Keong Thong Shamsul Mohd Zain Rosmawati Mohamed 《PloS one》2013,8(4)
Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by elevations in total cholesterol (TC) and low density lipoprotein cholesterol (LDLc). Development of FH can result in the increase of risk for premature cardiovascular diseases (CVD). FH is primarily caused by genetic variations in Low Density Lipoprotein Receptor (LDLR), Apolipoprotein B (APOB) or Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) genes. Although FH has been extensively studied in the Caucasian population, there are limited reports of FH mutations in the Asian population. We investigated the association of previously reported genetic variants that are involved in lipid regulation in our study cohort. A total of 1536 polymorphisms previously implicated in FH were evaluated in 141 consecutive patients with clinical FH (defined by the Dutch Lipid Clinic Network criteria) and 111 unrelated control subjects without FH using high throughput microarray genotyping platform. Fourteen Single Nucleotide Polymorphisms (SNPs) were found to be significantly associated with FH, eleven with increased FH risk and three with decreased FH risk. Of the eleven SNPs associated with an increased risk of FH, only one SNP was found in the LDLR gene, seven in the APOB gene and three in the PCSK9 gene. SNP rs12720762 in APOB gene is associated with the highest risk of FH (odds ratio 14.78, p<0.001). Amongst the FH cases, 108 out of 141 (76.60%) have had at least one significant risk-associated SNP. Our study adds new information and knowledge on the genetic polymorphisms amongst Asians with FH, which may serve as potential markers in risk prediction and disease management. 相似文献
106.
107.
108.
Xiuhong Feng Dayana Rodriguez‐Contreras Tamsen Polley Lon‐Fye Lye David Scott Richard J.S. Burchmore Stephen M. Beverley Scott M. Landfear 《Molecular microbiology》2013,87(2):412-429
The genome of Leishmania mexicana encompasses a cluster of three glucose transporter genes designated LmxGT1, LmxGT2 and LmxGT3. Functional and genetic studies of a cluster null mutant (Δlmxgt1‐3) have dissected the roles of these proteins in Leishmania metabolism and virulence. However, null mutants were recovered at very low frequency, and comparative genome hybridizations revealed that Δlmxgt1‐3 mutants contained a linear extrachromosomal 40 kb amplification of a region on chromosome 29 not amplified in wild type parasites. These data suggested a model where this 29‐40k amplicon encoded a second site suppressor contributing to parasite survival in the absence of GT1‐3 function. To test this, we quantified the frequency of recovery of knockouts in the presence of individual overexpressed open reading frames covering the 29‐40k amplicon. The data mapped the suppressor activity to PIFTC3, encoding a component of the intraflagellar transport pathway. We discuss possible models by which PIFTC3 might act to facilitate loss of GTs specifically. Surprisingly, by plasmid segregation we showed that continued PIFTC3 overexpression was not required for Δlmxgt1‐3 viability. These studies provide the first evidence that genetic suppression can occur by providing critical biological functions transiently. This novel form of genetic suppression may extend to other genes, pathways and organisms. 相似文献
109.
110.
Huey-Shi Lye Boon-Yin Khoo Abdul Alias Karim Gulam Rusul Min-Tze Liong 《Annals of microbiology》2013,63(2):615-622
The aim of this study was to evaluate the sub-lethal effect of ultraviolet radiation (UV) on the cell growth, intestinal adherence ability and cholesterol removal potential of parent cells and the possible inheritance of such effects on subsequent sub-cultures of Lactobacillus acidophilus BT 1088 cells under conditions that mimic the human gastrointestinal tract. We found that UV decreased (P?<?0.05) growth of the parent cells immediately upon treatment (0 h), although an increase (P?<?0.05) in growth was observed at 8–24 h of fermentation compared to that of the control. The intestinal adherence ability of the parent cells decreased significantly by 15.62 % (P?<?0.05) compared to that of the control. Nevertheless, UV led to increased (>26.22 %; P?<?0.05) cholesterol removal from the parent cells, accompanied by an increased incorporation of cholesterol into the cellular membrane and an increased ratio of membrane cholesterol:phospholipids (C:P; P?<?0.05; 95 % confidence interval 8.71–121.95 %) in parent cells, compared to that of the control. Incorporated cholesterol was found in the interface of apolar and polar regions, polar heads and also apolar tails of phospholipids in the cellular membrane bilayer. However, such traits were not inherited by the treated cells in subsequent sub-cultures (first, second and third sub-culture). Our data suggest that UV could be a potential physical treatment to increase the cholesterol removal ability of parent cells without inducing permanent damage to the treated cells. UV treatment did not affect the intestinal adherence functionality of the treated cells in subsequent sub-cultures. 相似文献