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排序方式: 共有353条查询结果,搜索用时 15 毫秒
71.
There is an urgent need for novel biomarkers that can be used to improve the diagnosis, predict the disease progression, improve our understanding of the pathology or serve as therapeutic targets for neurodegenerative diseases. Cerebrospinal fluid (CSF) is in direct contact with the CNS and reflects the biochemical state of the CNS under different physiological and pathological settings. Because of this, CSF is regarded as an excellent source for identifying biomarkers for neurological diseases and other diseases affecting the CNS. Quantitative proteomics and sophisticated computational software applied to analyze the protein content of CSF has been fronted as an attractive approach to find novel biomarkers for neurological diseases. This review will focus on some of the potential pitfalls in biomarker studies using CSF, summarize the status of the field of CSF proteomics in general, and discuss some of the most promising proteomics biomarker study approaches. A brief status of the biomarker discovery efforts in multiple sclerosis, Alzheimer's disease, and Parkinson's disease is also given. 相似文献
72.
Functional significance of isoform diversification in the protocadherin gamma gene cluster 总被引:1,自引:0,他引:1
WV Chen FJ Alvarez JL Lefebvre B Friedman C Nwakeze E Geiman C Smith CA Thu JC Tapia B Tasic JR Sanes T Maniatis 《Neuron》2012,75(3):402-409
The mammalian Protocadherin (Pcdh) alpha, beta, and gamma gene clusters encode a large family of cadherin-like transmembrane proteins that are differentially expressed in individual neurons. The 22 isoforms of the Pcdhg gene cluster are diversified into A-, B-, and C-types, and the C-type isoforms differ from all other clustered Pcdhs in sequence and expression. Here, we show that mice lacking the three C-type isoforms are phenotypically indistinguishable from the Pcdhg null mutants, displaying virtually identical cellular and synaptic alterations resulting from neuronal apoptosis. By contrast, mice lacking three A-type isoforms exhibit no detectable phenotypes. Remarkably, however, genetically blocking apoptosis rescues the neonatal lethality of the C-type isoform knockouts, but not that of the Pcdhg null mutants. We conclude that the role of the Pcdhg gene cluster in neuronal survival is primarily, if not specifically, mediated by its C-type isoforms, whereas a separate role essential for postnatal development, likely in neuronal wiring, requires isoform diversity. 相似文献
73.
The liver peptide hepcidin regulates body iron, is upregulated in iron overload and inflammation, and is downregulated in iron deficiency/hypoxia. The transmembrane serine protease matriptase-2 (TMPRSS6) inhibits the hepcidin response and its mutational inactivation causes iron-deficient anemia in mice and humans. Here we confirm the inhibitory effect of matriptase-2 on hepcidin promoter; we show that matriptase-2 lacking the serine protease domain, identified in the anemic Mask mouse (matriptase-2(MASK)), is fully inactive and that mutant R774C found in patients with genetic iron deficiency has decreased inhibitory activity. Matriptase-2 cleaves hemojuvelin (HJV), a regulator of hepcidin, on plasma membrane; matriptase-2(MASK) shows no cleavage activity and the human mutant only partial cleavage capacity. Matriptase-2 interacts with HJV through the ectodomain since the interaction is conserved in matriptase-2(MASK). The expression of matriptase-2 mutants in zebrafish results in anemia, confirming the matriptase-2 role in iron metabolism and its interaction with HJV. 相似文献
74.
中华绒螯蟹卵巢差减cDNA文库的构建 总被引:17,自引:0,他引:17
应用抑制性差减杂交技术构建中华绒螯蟹卵巢两个发育时期的差减cDNA文库。正向差减杂交以Ⅲ期卵巢为试验方、Ⅱ期卵巢为驱动方,反向差减杂交以Ⅱ期卵巢为试验方、Ⅲ期卵巢为驱动方;将所获差减cDNA片段克隆入质粒表达载体,转化大肠杆菌JM109。最后获得的正、反向差减文库分别含863、360个重组子。PCR扩增鉴定正、反向差减cDNA文库的插入片段平均大小分别为360和160bp,表明所构建的差减言语库适合进一步研究中华绒螯蟹卵巢发育相关基因。 相似文献
75.
76.
Aye Aye Mar Erika L. Szotek Ali Koohang William P. Flavin David A. Eiznhamer Michael T. Flavin Ze-Qi Xu 《Bioorganic & medicinal chemistry letters》2010,20(18):5389-5393
Apoptosis is a highly regulated process by which excessive cells are eliminated in order to maintain normal cell development and tissue homeostasis. Resistance to apoptosis often contributes to failure in cancer prevention and treatment. Apoptotic cell death regulators are considered important targets for discovery and development of new therapeutic agents in oncology research. A class of novel aza-lupane triterpenoids were designed, synthesized, and evaluated for antitumor activity against a panel of cancer cell lines of different histogenic origin and for ability to induce apoptosis. 3,30-Bis(aza) derivatives were identified not only to possess improved cytotoxicity compared to the natural product betulinic acid but also to affect cell death predominantly via apoptosis, whereas the mono(aza) derivatives apparently triggered cell death via different, non-apoptotic pathway(s). 相似文献
77.
78.
Zhu YZ Chong CL Chuah SC Huang SH Nai HS Tong HT Whiteman M Moore PK 《American journal of physiology. Heart and circulatory physiology》2006,290(2):H517-H524
We aimed to determine whether nitroparacetamol (NO-paracetamol) and paracetamol exhibit cardioprotective effects. Myocardial infarction (MI) was induced in rats, and drug treatment was started 1 wk before surgery. Mortality rate and infarct size at 2 days after MI were compared. Treatment groups included vehicle (saline), paracetamol (5 mg x kg(-1) x day(-1)) and NO-paracetamol (15 mg x kg(-1) x day(-1)). Mortality rates for vehicle (n = 80), paracetamol (n = 79), and NO-paracetamol (n = 76) groups were 37.5%, 21.5%, and 26.3%, respectively. Infarct size for the vehicle group was 44.8% (+/-6.1%) of the left ventricle (LV). For the paracetamol and NO-paracetamol groups, infarct size was 31.3% (+/-5.6%) and 30.7% (+/-8.1%) of the LV, respectively. Both paracetamol- and NO-paracetamol-treated groups showed increased activities of catalase and SOD compared with the vehicle group. They could attenuate endothelial, inducible, and neuronal nitric oxide synthase and cyclooxygenase-1 and -2 gene expression after MI. The observation indicates the potential clinical significance of the cardioprotective effects of these drugs. 相似文献
79.
Sein Lwin Yasuo Inoshima Yasuro Atoji Hiroshi Ueno Naotaka Ishiguro 《Cell and tissue research》2009,338(3):343-354
We have previously reported the early uptake and transport of foreign particles into Peyer’s patches (PPs) of newborn and
2-month-old calves and shown that the peak uptake of particles occurs 6 h after inoculation, in addition to site- and size-related
effects on particle uptake. We now report the distribution of immune cells within PPs of the distal ileum in newborn and 2-month-old
calves inoculated with carbon black. The types of immune cells involved in the early uptake and transport of recombinant mouse
prion protein (rMPrP) within PPs of newborn calf were investigated by using monoclonal antibodies CD11c, CD14, CD68, CD172a,
and CD21. CD11c+, CD14+, CD68+, CD172a+, and CD21+ immune cells were widely distributed in four tissue compartments (villi, dome, interfollicular region, and follicles) of
PPs in the distal ileum of newborn and 2-month-old calves, whereas CD11c+, CD14+, CD172a+, and CD21+ immune cells were more prominently distributed in the dome areas of newborn calves than in 2-month-old calves. Moreover,
CD11c+ and CD14+ dendritic cells, CD172a+ and CD68+ macrophages, and CD21+ follicular dendritic cells containing rMPrP were primarily observed in the dome and inner follicular regions. The deposition
of rMPrP within CD11c+, CD14+, CD172a+, and CD68+ cells, but not CD21+ cells, was detected in villous regions. rMPrP-positive immune cells within the interfollicular regions included only CD11c+ and CD172+ cells. Although the particles used in this investigation do not include the infectious prion protein, PrPSc, our experimental setup provides a useful model for studying immune cells involved in the early uptake and transport of PrPSc. 相似文献
80.