全文获取类型
收费全文 | 383篇 |
免费 | 18篇 |
出版年
2024年 | 1篇 |
2023年 | 2篇 |
2022年 | 3篇 |
2021年 | 13篇 |
2020年 | 5篇 |
2019年 | 8篇 |
2018年 | 14篇 |
2017年 | 7篇 |
2016年 | 13篇 |
2015年 | 15篇 |
2014年 | 15篇 |
2013年 | 27篇 |
2012年 | 25篇 |
2011年 | 31篇 |
2010年 | 21篇 |
2009年 | 23篇 |
2008年 | 24篇 |
2007年 | 26篇 |
2006年 | 23篇 |
2005年 | 21篇 |
2004年 | 21篇 |
2003年 | 17篇 |
2002年 | 14篇 |
2001年 | 5篇 |
2000年 | 1篇 |
1999年 | 5篇 |
1998年 | 4篇 |
1997年 | 2篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1981年 | 1篇 |
1977年 | 2篇 |
1976年 | 2篇 |
排序方式: 共有401条查询结果,搜索用时 265 毫秒
61.
62.
Impact of heavy metals on enzymatic activity of substrate and on composting worms Eisenia fetida 总被引:4,自引:0,他引:4
The effect of heavy metals Cu and Zn on dehydrogenase and protease activity of the substrate during vermicomposting was investigated. Three dosages of Cu and Zn were tested in mesocosm experiments to investigate their bioaccumulation and impact on the reproduction of Eisenia fetida. Cu accumulated within the worm tissues in dosage concentrations up to a maximum level of 213 mg Cu kg(-1). The number of juveniles decreased from the lowest to highest dosages of Cu and Zn after 10 weeks of the experiment. Dehydrogenase showed a strong negative correlation (P < 0.01) with increased dosage of Cu, while protease remained unaffected. An overall reduction on dehydrogenase activity with increasing dosages of Cu and Zn indicated that these metals would impact detrimentally on the soil microbiology and consequently the stabilisation of the dosed media. 相似文献
63.
Kumar JS Majo VJ Sullivan GM Prabhakaran J Simpson NR Van Heertum RL Mann JJ Parsey RV 《Bioorganic & medicinal chemistry》2006,14(12):4029-4034
Synthesis and evaluation of [O-methyl-11C](4-methoxy-2-methylphenyl)[1-(1-methoxymethylpropyl)-6-methyl-1H-[1,2,3]triazolo[4,5-c]pyridin-4-yl]amine or [11C]SN003 ([11C]6), as a PET imaging agent for CRF1 receptors, in baboons is described. 4-[1-(1-Methoxymethylpropyl)-6-methyl-1H-[1,2,3]triazolo[4,5-c]pyridin-4-ylamino]-3-methylphenol (5), the precursor molecule for the radiolabeling, was synthesized from 2,4-dichloro-6-methyl-3-nitropyridine in seven steps with 20% overall yield. The total time required for the synthesis of [11C]SN003 is 30 min from EOB using [11C]methyl triflate in the presence of NaOH in acetone. The yield of the synthesis is 22% (EOS) with >99% chemical and radiochemical purities and a specific activity of >2000 Ci/mmol. PET studies in baboon show that [11C]6 penetrates the BBB and accumulates in brain. No detectable specific binding was observed, likely due to the rapid metabolism or low density of CRF1 receptors in primate brain. 相似文献
64.
Jaya Kishor Seth Sanmitra Roy Sameer Sura Dilraj Puvala Subhrendu Sekhar Mishra Anil Mohapatra 《Journal of fish biology》2024,104(3):548-563
A new species of the genus Awaous (Oxudercidae), Awaous motla sp. nov., is described based on 18 specimens collected from the Mahanadi River near Sonepur, Subarnapur District, and 3 specimens from the same river near Boudh bridge, Boudh District of Odisha, India. This species is distinct from its congeners by having a combination of characteristics: relatively small eyes, diameter of 6.6–8.4 in head length (LH); robust and long snout, 2.0–2.6 in LH; eye diameter 2.7–4.1 in snout length; cephalic sensory pore system interrupted with eight pores; predorsal scales 13–15; longitudinal scale series 55–58; gill rakers 2 + 1 + (6–7) on the first gill arch; teeth small, conical, and in a single row on the upper jaw and multiserial (2–3) on the lower jaw. This species is also differentiated from some of its congeners in the nucleotide composition of the cytochrome c oxidase I gene by 8.3%–13.8% Kimura two-parameter (K2P) distance and belongs to a separate cluster in the maximum likelihood tree analysis. This finding is also supported by the species delimitation analysis based on Assemble Species by Automatic Partitioning. The new species holds high commercial value in its locality and needs special conservation attention for sustainable utilization. 相似文献
65.
Vibha Jha Creg J. Workman Tracy L. McGaha Liping Li Jaya Vas Dario A. A. Vignali Marc Monestier 《PloS one》2014,9(8)
Environmental factors including drugs, mineral oils and heavy metals such as lead, gold and mercury are triggers of autoimmune diseases in animal models or even in occupationally exposed humans. After exposure to subtoxic levels of mercury (Hg), genetically susceptible strains of mice develop an autoimmune disease characterized by the production of highly specific anti-nucleolar autoantibodies, hyperglobulinemia and nephritis. However, mice can be tolerized to the disease by a single low dose administration of Hg. Lymphocyte Activation Gene-3 (LAG-3) is a CD4-related, MHC-class II binding molecule expressed on activated T cells and NK cells which maintains lymphocyte homeostatic balance via various inhibitory mechanisms. In our model, administration of anti-LAG-3 monoclonal antibody broke tolerance to Hg resulting in autoantibody production and an increase in serum IgE level. In addition, LAG-3-deficient B6.SJL mice not only had increased susceptibility to Hg-induced autoimmunity but were also unresponsive to tolerance induction. Conversely, adoptive transfer of wild-type CD4+ T cells was able to partially rescue LAG-3-deficient mice from the autoimmune disease. Further, in LAG-3-deficient mice, mercury elicited higher amounts of IL-6, IL-4 and IFN-γ, cytokines known to play a critical role in mercury-induced autoimmunity. Therefore, we conclude that LAG-3 exerts an important regulatory effect on autoimmunity elicited by a common environmental pollutant. 相似文献
66.
Madhuja Samaddar Arvind Vittal Goswami Jaya Purushotham Pushpa Hegde Patrick D'Silva 《Molecular biology of the cell》2014,25(14):2129-2142
Mitochondrial Hsp70 (mtHsp70) is essential for a vast repertoire of functions, including protein import, and requires effective interdomain communication for efficient partner-protein interactions. However, the in vivo functional significance of allosteric regulation in eukaryotes is poorly defined. Using integrated biochemical and yeast genetic approaches, we provide compelling evidence that a conserved substrate-binding domain (SBD) loop, L4,5, plays a critical role in allosteric communication governing mtHsp70 chaperone functions across species. In yeast, a temperature-sensitive L4,5 mutation (E467A) disrupts bidirectional domain communication, leading to compromised protein import and mitochondrial function. Loop L4,5 functions synergistically with the linker in modulating the allosteric interface and conformational transitions between SBD and the nucleotide-binding domain (NBD), thus regulating interdomain communication. Second-site intragenic suppressors of E467A isolated within the SBD suppress domain communication defects by conformationally altering the allosteric interface, thereby restoring import and growth phenotypes. Strikingly, the suppressor mutations highlight that restoration of communication from NBD to SBD alone is the minimum essential requirement for effective in vivo function when primed at higher basal ATPase activity, mimicking the J-protein–bound state. Together these findings provide the first mechanistic insights into critical regions within the SBD of mtHsp70s regulating interdomain communication, thus highlighting its importance in protein translocation and mitochondrial biogenesis. 相似文献
67.
Andrea M. Weckman Andrea L. Conroy Mwayiwawo Madanitsa Bruno Gnaneswaran Chloe R. McDonald Linda Kalilani-Phiri Jaya Chandna Doreen Ali Victor Mwapasa Carole Khairallah Kyaw Lay Thwai Steven R. Meshnick Steve M. Taylor Feiko O. ter Kuile Kevin C. Kain Melissa Gladstone 《PLoS medicine》2021,18(9)
BackgroundAnnually 125 million pregnancies are at risk of malaria infection. However, the impact of exposure to malaria in pregnancy on neurodevelopment in children is not well understood. We hypothesized that malaria in pregnancy and associated maternal immune activation result in neurodevelopmental delay in exposed offspring.Methods and findingsBetween April 2014 and April 2015, we followed 421 Malawian mother–baby dyads (median [IQR] maternal age: 21 [19, 28] years) who were previously enrolled (median [IQR] gestational age at enrollment: 19.7 [17.9, 22.1] weeks) in a randomized controlled malaria prevention trial with 5 or 6 scheduled assessments of antenatal malaria infection by PCR. Children were evaluated at 12, 18, and/or 24 months of age with cognitive tests previously validated in Malawi: the Malawi Developmental Assessment Tool (MDAT) and the MacArthur–Bates Communicative Development Inventories (MCAB-CDI). We assessed the impact of antenatal malaria (n [%] positive: 240 [57.3]), placental malaria (n [%] positive: 112 [29.6]), and maternal immune activation on neurocognitive development in children. Linear mixed-effects analysis showed that children exposed to antenatal malaria between 33 and 37 weeks gestation had delayed language development across the 2-year follow-up, as measured by MCAB-CDI (adjusted beta estimate [95% CI], −7.53 [−13.04, −2.02], p = 0.008). Maternal immune activation, characterized by increased maternal sTNFRII concentration, between 33 and 37 weeks was associated with lower MCAB-CDI language score (adjusted beta estimate [95% CI], −8.57 [−13.09, −4.06], p < 0.001). Main limitations of this study include a relatively short length of follow-up and a potential for residual confounding that is characteristic of observational studies.ConclusionsThis mother–baby cohort presents evidence of a relationship between malaria in pregnancy and neurodevelopmental delay in offspring. Malaria in pregnancy may be a modifiable risk factor for neurodevelopmental injury independent of birth weight or prematurity. Successful interventions to prevent malaria during pregnancy may reduce the risk of neurocognitive delay in children.Andrea Weckman and co-workers study associations between children’s neurodevelopmental outcomes and malaria in pregnancy. 相似文献
68.
Shailly Anand Sukanya Lal Utkarsh Sood Vipin Gupta Gauri Garg Dhingra Renu Solanki Jasvinder Kaur Roshan Kumar Anjali Saxena Ankita Dua Charu Tripathi Chandni Talwar Charu Dogra Rawat Harpreet Kaur Helianthous Verma Jaspreet Kaur Mansi Verma Mona Singh Princy Hira Nirjara Singhvi Nitish Kumar Mahato Om Prakash Jaya Malhotra Rup Lal Vipin Chandra Kalia 《Indian journal of microbiology》2021,61(4):397
69.
Madhuri S. Salker Jaya Nautiyal Jennifer H. Steel Zoe Webster Sandra ?u?urovi? Marilena Nicou Yogesh Singh Emma S. Lucas Keisuke Murakami Yi-Wah Chan Sean James Yazan Abdallah Mark Christian B. Anne Croy Biserka Mulac-Jericevic Siobhan Quenby Jan J. Brosens 《PloS one》2012,7(12)
Decidualization renders the endometrium transiently receptive to an implanting blastocyst although the underlying mechanisms remain incompletely understood. Here we show that human endometrial stromal cells (HESCs) rapidly release IL-33, a key regulator of innate immune responses, upon decidualization. In parallel, differentiating HESCs upregulate the IL-33 transmembrane receptor ST2L and other pro-inflammatory mediators before mounting a profound anti-inflammatory response that includes downregulation of ST2L and increased expression of the soluble decoy receptor sST2. We demonstrate that HESCs secrete factors permissive of embryo implantation in mice only during the pro-inflammatory phase of the decidual process. IL-33 knockdown in undifferentiated HESCs was sufficient to abrogate this pro-inflammatory decidual response. Further, sequential activation of the IL-33/ST2L/sST2 axis was disordered in decidualizing HESCs from women with recurrent pregnancy loss. Signals from these cultures prolonged the implantation window but also caused subsequent pregnancy failure in mice. Thus, Il-33/ST2 activation in HESCS drives an autoinflammatory response that controls the temporal expression of receptivity genes. Failure to constrain this response predisposes to miscarriage by allowing out-of-phase implantation in an unsupportive uterine environment. 相似文献
70.