全文获取类型
收费全文 | 227篇 |
免费 | 34篇 |
出版年
2021年 | 3篇 |
2018年 | 2篇 |
2017年 | 2篇 |
2016年 | 5篇 |
2015年 | 5篇 |
2014年 | 10篇 |
2013年 | 12篇 |
2012年 | 15篇 |
2011年 | 21篇 |
2010年 | 12篇 |
2009年 | 6篇 |
2008年 | 11篇 |
2007年 | 12篇 |
2006年 | 8篇 |
2005年 | 5篇 |
2004年 | 5篇 |
2003年 | 4篇 |
2002年 | 5篇 |
2001年 | 6篇 |
2000年 | 8篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1994年 | 5篇 |
1993年 | 1篇 |
1992年 | 7篇 |
1991年 | 10篇 |
1990年 | 5篇 |
1989年 | 7篇 |
1988年 | 5篇 |
1987年 | 9篇 |
1986年 | 5篇 |
1985年 | 5篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1978年 | 2篇 |
1976年 | 2篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 2篇 |
1970年 | 2篇 |
1969年 | 1篇 |
1963年 | 1篇 |
1960年 | 1篇 |
1959年 | 1篇 |
1953年 | 1篇 |
排序方式: 共有261条查询结果,搜索用时 15 毫秒
91.
Charlotte?J. Sumner Constantin d’Ydewalle Joe Wooley Katherine?A. Fawcett Dena Hernandez Alice?R. Gardiner Bernadett Kalmar Robert?H. Baloh Michael Gonzalez Stephan Züchner Horia?C. Stanescu Robert Kleta Ami Mankodi David?R. Cornblath Kevin?B. Boylan Mary?M. Reilly Linda Greensmith Andrew?B. Singleton Matthew?B. Harms Alexander?M. Rossor Henry Houlden 《American journal of human genetics》2013,93(5):976-983
92.
Carolyn B. Boylan Carol A. Bennett-Clarke Nicholas L. Chiaia Robert W. Rhoades 《Somatosensory & motor research》2013,30(1):52-60
Immunocytochemical and autoradiographic techniques were employed to determine the time course of expression of the serotonin (5-HT) transporter (SERT) on thalamocortical afferents in the rat's primary somatosensory cortex (S-I), and to correlate this expression to the transient vibrissae-related patterning of 5-HT immunostaining previously described. In additional in vivo and in vitro experiments, 5-HT and 3 H-5-HT were applied directly to the cortices of untreated and 5,7-dihydroxytryptamine-treated (5,7-DHT) rats in order to determine the period during which SERT functions on thalamocortical axons to take up 5-HT. In postnatal rats, SERT immunohistochemistry revealed a somatotopic patterning in S-I that persisted until P-15, which is 6 days after the disappearance of the vibrissae-related 5-HT immunostaining. 3 H-citalopram autoradiography revealed a vibrissae-related pattern in layer IV of S-I until at least P-30. Following destruction of raphe-cortical afferents with 5,7-DHT on the day of birth, this binding pattern remained visible until at least P-25, indicating that SERT located on thalamocortical axons is responsible for the 3 H-citalopram patterning observed in S-I. Tissue from 5,7-DHT-treated rats that had 5-HT applied directly to their cortices revealed a normal vibrissae-related pattern of 5-HT immunostaining in S-I at P-7 and P-11 but only a faint pattern at P-13 and none at P-14. In addition, 3 H-5-HT injected directly into S-I labeled layer IV barrels at P-6 and P-12 but not at P-18. The results of these experiments demonstrate that SERT is expressed by thalamocortical afferents and remains functional long after the vibrissae-related 5-HT immunostaining in cortex disappears. 相似文献
93.
AbstractAqueous low molecular weight organic carbon-14 (14C) substances can be formed by the oxidation of carbide and impurities within nuclear fuel cladding. During reprocessing and interim storage 14C-labeled organic compounds may leak to the shallow subsurface environments at nuclear facilities where denitrifying and iron reducing zones can exist. 14C-labeled organic compounds (acetate, formate, formaldehyde and methanol) were used as electron donors in microcosm experiments, under both denitrification and iron reduction, using glacial outwash sediments and groundwater composition representative of the Sellafield nuclear reprocessing site, UK. In denitrifying microcosms, <6% of the initial 14C-DOC remained 15?days after injection into the microcosm irrespective of the electron donor; with concurrent 14CO2 (g) production. Lack of removal in sterile controls suggests that 14C-organics were metabolized by microorganisms. Under iron-reducing conditions both 14C-carboxylates were removed from solution rapidly, but some formaldehyde and methanol remained in solution 32?days after injection into the microcosm so there is potential that a proportion of 14C-formaldehyde and 14C-methanol may persist for longer in subsurface environments. 相似文献
94.
Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS 总被引:3,自引:0,他引:3
DeJesus-Hernandez M Mackenzie IR Boeve BF Boxer AL Baker M Rutherford NJ Nicholson AM Finch NA Flynn H Adamson J Kouri N Wojtas A Sengdy P Hsiung GY Karydas A Seeley WW Josephs KA Coppola G Geschwind DH Wszolek ZK Feldman H Knopman DS Petersen RC Miller BL Dickson DW Boylan KB Graff-Radford NR Rademakers R 《Neuron》2011,72(2):245-256
95.
Nguyen KT Wu JC Boylan JA Gherardini FC Pei D 《Archives of biochemistry and biophysics》2007,468(2):217-225
Peptide deformylase (PDF, E.C. 3.5.1.88) catalyzes the removal of N-terminal formyl groups from nascent ribosome-synthesized polypeptides. PDF contains a catalytically essential divalent metal ion, which is tetrahedrally coordinated by three protein ligands (His, His, and Cys) and a water molecule. Previous studies revealed that the metal cofactor is a Fe2+ ion in Escherichia coli and many other bacterial PDFs. In this work, we found that PDFs from two iron-deficient bacteria, Borrelia burgdorferi and Lactobacillus plantarum, are stable and highly active under aerobic conditions. The native B. burgdorferi PDF (BbPDF) was purified 1200-fold and metal analysis revealed that it contains ∼1.1 Zn2+ ion/polypeptide but no iron. Our studies suggest that PDF utilizes different metal ions in different organisms. These data have important implications in designing PDF inhibitors and should help address some of the unresolved issues regarding PDF structure and catalytic function. 相似文献
96.
Goel R Boylan B Gruman L Newman PJ North PE Newman DK 《American journal of physiology. Gastrointestinal and liver physiology》2007,293(6):G1205-G1214
The severity of nonalcoholic steatohepatitis (NASH) is determined by environmental and genetic factors, the latter of which are incompletely characterized. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a 130-kDa transmembrane glycoprotein expressed on blood and vascular cells. In the present study, we provide data for the novel finding that genetic deficiency of PECAM-1 potentiates the development and progression of NASH. We found that the rate of development and severity of diet-induced NASH are markedly enhanced in PECAM-1-deficient [knockout (KO)] mice relative to wild-type (WT) mice, as measured by histological and biochemical evaluation. Livers from KO mice exhibited typical histological features of NASH, including macrovesicular fat accumulation, hepatocyte injury with infiltration of inflammatory cells, fibrosis, and heightened oxidative stress. Alanine aminotransferase, a marker for liver injury, was also significantly higher in KO compared with WT mice. Consistent with a role for PECAM-1 as a suppressor of proinflammatory cytokines, plasma levels of inflammatory cytokines, including TNF-alpha and monocyte chemoattractant protein-1 (MCP-1), were also significantly higher in KO compared with WT mice. These findings are the first to show that the PECAM-1-deficient mouse develops progressive nonalcoholic fatty liver disease (NAFLD), supporting a role for PECAM-1 as a negative regulator of NAFLD progression. Future examination of recently identified PECAM-1 allelic isoforms in humans as potential risk factors for developing NASH may be warranted. 相似文献
97.
Pauline?AaltenEmail author Inez?HGB?Ramakers Geert?Jan?Biessels Peter?Paul?de Deyn Huiberdina?L?Koek Marcel?GM?OldeRikkert Ania?M?Oleksik Edo?Richard Lieke?L?Smits John?C?van Swieten Laura?K?Teune Aad?van der Lugt Frederik?Barkhof Charlotte?E?Teunissen Nico?Rozendaal Frans?RJ?Verhey Wiesje?M?van der Flier 《BMC neurology》2014,14(1):254
98.
99.
Sielecki TM Johnson TL Liu J Muckelbauer JK Grafstrom RH Cox S Boylan J Burton CR Chen H Smallwood A Chang CH Boisclair M Benfield PA Trainor GL Seitz SP 《Bioorganic & medicinal chemistry letters》2001,11(9):1157-1160
Quinazolines have been identified as inhibitors of CDK4/D1 and CDK2/E. Aspects of the SAR were investigated using solution-phase, parallel synthesis. An X-ray crystal structure was obtained of quinazoline 51 bound in CDK2 and key interactions within the ATP binding pocket are defined. 相似文献
100.
Acid α-glucosidase (GAA) is a lysosomal enzyme that hydrolyzes glycogen to glucose. Deficiency of GAA causes Pompe disease. Mammalian GAA is synthesized as a precursor of ~ 110,000 Da that is N-glycosylated and targeted to the lysosome via the M6P receptors. In the lysosome, human GAA is sequentially processed by proteases to polypeptides of 76-, 19.4-, and 3.9-kDa that remain associated. Further cleavage between R200 and A204 inefficiently converts the 76-kDa polypeptide to the mature 70-kDa form with an additional 10.4-kDa polypeptide. GAA maturation increases its affinity for glycogen by 7-10 fold. In contrast to human GAA, processing of bovine and hamster GAA to the 70-kDa form is more rapid. A comparison of sequences surrounding the cleavage site revealed human GAA contains histidine at 201 while other species contain hydrophobic amino acids at position 201 in the otherwise conserved sequence. Recombinant human GAA (rhGAA) containing the H201L substitution was expressed in 293 T cells by transfection. Pulse chase experiments in 293 T cells expressing rhGAA with or without the H201L substitution revealed rapid processing of rhGAAH201L but not rhGAAWT to the 70-kDa form. Similarly, when GAA precursor was endocytosed by human Pompe fibroblasts rhGAAH201L but not rhGAAWT was rapidly converted to the 70-kDa mature GAA. These studies indicate that the amino acid at position 201 influences the rate of conversion of 76-kDa GAA to 70-kDa GAA. The GAA sequence rather than the lysosomal protease environment explains the predominance of the 76-kDa form in human tissues. 相似文献