全文获取类型
收费全文 | 591篇 |
免费 | 105篇 |
专业分类
696篇 |
出版年
2021年 | 5篇 |
2020年 | 6篇 |
2019年 | 5篇 |
2017年 | 9篇 |
2016年 | 12篇 |
2015年 | 8篇 |
2014年 | 13篇 |
2013年 | 20篇 |
2012年 | 24篇 |
2011年 | 15篇 |
2010年 | 16篇 |
2009年 | 15篇 |
2008年 | 19篇 |
2007年 | 19篇 |
2006年 | 20篇 |
2005年 | 21篇 |
2004年 | 15篇 |
2003年 | 12篇 |
2002年 | 16篇 |
2001年 | 10篇 |
2000年 | 14篇 |
1999年 | 22篇 |
1998年 | 16篇 |
1997年 | 8篇 |
1996年 | 7篇 |
1995年 | 6篇 |
1994年 | 13篇 |
1993年 | 8篇 |
1992年 | 41篇 |
1991年 | 23篇 |
1990年 | 31篇 |
1989年 | 26篇 |
1988年 | 14篇 |
1987年 | 15篇 |
1986年 | 15篇 |
1985年 | 7篇 |
1984年 | 6篇 |
1983年 | 6篇 |
1982年 | 9篇 |
1980年 | 8篇 |
1979年 | 11篇 |
1978年 | 12篇 |
1977年 | 6篇 |
1975年 | 6篇 |
1974年 | 5篇 |
1973年 | 10篇 |
1971年 | 6篇 |
1970年 | 6篇 |
1969年 | 6篇 |
1966年 | 4篇 |
排序方式: 共有696条查询结果,搜索用时 31 毫秒
101.
102.
Glycine, a major inhibitory neurotransmitter in the vertebrate nervous system, not only functions in synaptic signaling, but has also been implicated in regulating neuronal differentiation, neuronal proliferation, synaptic modeling, and neural network stability. Elements of the glycinergic phenotype include the membrane-bound glycine transporters (GLYT1 and GLYT2), which remove glycine from the synaptic cleft, and the vesicular inhibitory amino acid transporter (VIAAT or VGAT), which sequesters both glycine and GABA into synaptic vesicles. Here, we describe the spatial and temporal expression patterns of xGlyT1, xGlyT2, and xVIAAT during early developmental stages of Xenopus laevis. In situ hybridization reveals that xGlyT1 is first expressed in early tailbud stages in the midbrain, hindbrain, and anterior spinal cord; it extends posteriorly through the spinal cord and appears in the forebrain, retina, between the somites, and in the blood islands by swimming tadpole stages. xGlyT2 and xVIAAT initially appear in late neurula stages in the anterior spinal cord. By swimming tadpole stages, the expression of these genes appears in the forebrain, midbrain, and hindbrain and extends posteriorly through the spinal cord; xVIAAT is also expressed in the retina. Confocal analysis of multiplex fluorescent in situ hybridization signal in the spinal cord reveals that xGlyT1 and xGlyT2 share little cellular colocalization. While there is significant coexpression between xVIAAT and xGlyT2, xVIAAT and the GABAergic marker glutamic acid decarboxylase (xGAD67), and xGlyT2 and xGAD67, each gene also appears to have discrete, non-colocalized areas of expression. 相似文献
103.
Raphael MP Christodoulides JA Qadri SN Qadri SA Miller MM Kurihara LK Byers JM 《Biosensors & bioelectronics》2008,24(4):894-898
Today's biosensors and drug delivery devices are increasingly incorporating lithographically patterned circuitry that is placed within microns of the biological molecules to be detected or released. Elevated temperatures due to Joule heating from the underlying circuitry cannot only reduce device performance, but also alter the biological activity of such molecules (i.e. binding, enzymatic, folding). As a consequence, biochip design and characterization will increasingly require local measurements of the temperature and temperature gradients on the biofunctionalized surface. We have developed a technique to address this challenge based on the use of DNA molecular beacons as a nanoscale temperature probe. The surface of fused-silica chips with lithographically patterned, current-carrying gold rings have been functionalized with a layer of molecular beacons. We utilize the temperature dependence of the molecular beacons to calibrate the temperature at the center of the rings as a function of applied current from 25 to 50 degrees C. The fluorescent images of the rings reveal the extent of heating to the surrounding chip due to the applied current while resolving temperature gradients over length scales of less than 500nm. Finite element analysis and analytic calculations of the distribution of heat in the vicinity of the current-carrying rings agree well with the experimental results. Thus, molecular beacons are shown to be a viable tool for temperature calibration of micron-sized circuitry and the visualization of submicron temperature gradients. 相似文献
104.
Kentsis A Reed C Rice KL Sanda T Rodig SJ Tholouli E Christie A Valk PJ Delwel R Ngo V Kutok JL Dahlberg SE Moreau LA Byers RJ Christensen JG Woude GV Licht JD Kung AL Staudt LM Look AT 《Nature medicine》2012,18(7):1118-1122
Although the treatment of acute myeloid leukemia (AML) has improved substantially in the past three decades, more than half of all patients develop disease that is refractory to intensive chemotherapy. Functional genomics approaches offer a means to discover specific molecules mediating the aberrant growth and survival of cancer cells. Thus, using a loss-of-function RNA interference genomic screen, we identified the aberrant expression of hepatocyte growth factor (HGF) as a crucial element in AML pathogenesis. We found HGF expression leading to autocrine activation of its receptor tyrosine kinase, MET, in nearly half of the AML cell lines and clinical samples we studied. Genetic depletion of HGF or MET potently inhibited the growth and survival of HGF-expressing AML cells. However, leukemic cells treated with the specific MET kinase inhibitor crizotinib developed resistance resulting from compensatory upregulation of HGF expression, leading to the restoration of MET signaling. In cases of AML where MET is coactivated with other tyrosine kinases, such as fibroblast growth factor receptor 1 (FGFR1), concomitant inhibition of FGFR1 and MET blocked this compensatory HGF upregulation, resulting in sustained logarithmic cell killing both in vitro and in xenograft models in vivo. Our results show a widespread dependence of AML cells on autocrine activation of MET, as well as the key role of compensatory upregulation of HGF expression in maintaining leukemogenic signaling by this receptor. We anticipate that these findings will lead to the design of additional strategies to block adaptive cellular responses that drive compensatory ligand expression as an essential component of the targeted inhibition of oncogenic receptors in human cancers. 相似文献
105.
Pierre P. Massion Yong Zou Hasmet Uner Porntip Kiatsimkul Holly J. Wolf Anna E. Baron Tim Byers Steinn Jonsson Stephen Lam Fred R. Hirsch York E. Miller Wilbur A. Franklin Marileila Varella-Garcia 《PloS one》2009,4(6)
Lung carcinoma development is accompanied by field changes that may have diagnostic significance. We have previously shown the importance of chromosomal aneusomy in lung cancer progression. Here, we tested whether genomic gains in six specific loci, TP63 on 3q28, EGFR on 7p12, MYC on 8q24, 5p15.2, and centromeric regions for chromosomes 3 (CEP3) and 6 (CEP6), may provide further value in the prediction of lung cancer. Bronchial biopsy specimens were obtained by LIFE bronchoscopy from 70 subjects (27 with prevalent lung cancers and 43 individuals without lung cancer). Twenty six biopsies were read as moderate dysplasia, 21 as severe dysplasia and 23 as carcinoma in situ (CIS). Four-micron paraffin sections were submitted to a 4-target FISH assay (LAVysion, Abbott Molecular) and reprobed for TP63 and CEP 3 sequences. Spot counts were obtained in 30–50 nuclei per specimen for each probe. Increased gene copy number in 4 of the 6 probes was associated with increased risk of being diagnosed with lung cancer both in unadjusted analyses (odds ratio = 11, p<0.05) and adjusted for histology grade (odds ratio = 17, p<0.05). The most informative 4 probes were TP63, MYC, CEP3 and CEP6. The combination of these 4 probes offered a sensitivity of 82% for lung cancer and a specificity of 58%. These results indicate that specific cytogenetic alterations present in preinvasive lung lesions are closely associated with the diagnosis of lung cancer and may therefore have value in assessing lung cancer risk. 相似文献
106.
Y S Fan R L Eddy M G Byers L L Haley W M Henry N J Nowak T B Shows 《Cytogenetics and cell genetics》1989,52(1-2):83-84
The gene for the human mineralocorticoid receptor (MLR) was previously localized to chromosome 4. Here, we have localized this gene to 4q31.2 by in situ hybridization. This precise mapping of MLR will assist in the linkage analysis and genetic characterization of pseudohypoaldosteronism, an autosomal recessive disorder which likely results from a defect in the MLR gene. 相似文献
107.
108.
109.
110.