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Rafael Nagler Ofer Ben-Izhak Dana Savulescu Ella Krayzler Sharon Akrish Svetlana Leschiner Irina Otradnov Sivan Zeno Leo Veenman Moshe Gavish 《生物化学与生物物理学报:疾病的分子基础》2010,1802(5):454-461
Oral cancer features high rates of mortality and morbidity, and is in dire need for new approaches. In the present study we analyzed 18 kDa translocator protein (TSPO) expression in oral (tongue) cancer tumors by immunohistochemistry. We also assayed TSPO binding in human tongue cancer cell lines and in the cellular fraction of saliva from tongue cancer patients, heavy cigarette smokers, and non-smoking healthy people as controls. Concurrently, TSPO protein levels, cell viability, mitochondrial membrane potential (Δψm), and general protein levels were analyzed. TSPO expression could be significantly enhanced in oral cancer tumors, compared to unaffected adjacent tissue. We also found that five-year survival probability dropped from 65% in patients with TSPO negative tumors to 7% in patients with highly expressed TSPO (p < 0.001). TSPO binding capacity was also pronounced in the human oral cancer cell lines SCC-25 and SCC-15 (3133 ± 643 fmol/mg protein and 6956 ± 549 fmol/mg protein, respectively). Binding decreased by 56% and 72%, in the SCC-25 and SCC-15 cell lines, respectively (p < 0.05) following CS exposure in cell culture. In the cellular fraction of saliva of heavy smokers TSPO binding was lower than in non-smokers (by 53%, p < 0.05). Also the cellular fraction of saliva exposed to CS in vitro showed decreased TSPO binding compared to unexposed saliva (by 30%, p < 0.001). Interestingly, oral cancer patients also displayed significantly lower TSPO binding in the cellular fraction of saliva compared to healthy controls (by 40%, p < 0.01). Our results suggest that low TSPO binding found in the cellular fraction of saliva may depend on genetic background as well as result from exposure to CS. We suggest that this may be related to a predisposition for occurrence of oral cancer. 相似文献
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Sharon Alane Abramowitz 《Culture, medicine and psychiatry》2010,34(2):353-379
The focus of this paper is the intercultural process through which Open Mole and trauma-related mental illnesses are brought
together in the postconflict mental health encounter. In this paper, I explore the historical dimension of this process by
reviewing the history of Open Mole, and the ways in which it has been interpreted, acted on, and objectified by external observers
over the last half-century. Moving into Liberia’s recent war and postconflict period, I examine the process by which Open
Mole is transformed from a culture-bound disorder into a local idiom of trauma, and how it has become a gateway diagnosis
of PTSD-related mental illnesses, and consider how it is produced as an objectified experience of psychiatric disorder in
clinical humanitarian contexts. By studying how Open Mole is transformed in the humanitarian encounter, I address the structure
and teleology of the humanitarian encounter and challenge some of the foundational assumptions about cultural sensitivity
and community-based mental health care in postconflict settings that are prevalent in scholarship and practice today. 相似文献
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Dikla Bandah-Rozenfeld Rob W.J. Collin Eyal Banin Karlien L.M. Coene Anna M. Siemiatkowska Lina Zelinger Dirk J. Lefeber Inbar Erdinest Francesca Simonelli Ellen A.W. Blokland Caroline C.W. Klaver Raheel Qamar Sandro Banfi Dror Sharon Anneke I. den Hollander 《American journal of human genetics》2010,87(2):199-208
Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases caused by progressive degeneration of the photoreceptor cells. Using autozygosity mapping, we identified two families, each with three affected siblings sharing large overlapping homozygous regions that harbored the IMPG2 gene on chromosome 3. Sequence analysis of IMPG2 in the two index cases revealed homozygous mutations cosegregating with the disease in the respective families: three affected siblings of Iraqi Jewish ancestry displayed a nonsense mutation, and a Dutch family displayed a 1.8 kb genomic deletion that removes exon 9 and results in the absence of seven amino acids in a conserved SEA domain of the IMPG2 protein. Transient transfection of COS-1 cells showed that a construct expressing the wild-type SEA domain is properly targeted to the plasma membrane, whereas the mutant lacking the seven amino acids appears to be retained in the endoplasmic reticulum. Mutation analysis in ten additional index cases that were of Dutch, Israeli, Italian, and Pakistani origin and had homozygous regions encompassing IMPG2 revealed five additional mutations; four nonsense mutations and one missense mutation affecting a highly conserved phenylalanine residue. Most patients with IMPG2 mutations showed an early-onset form of RP with progressive visual-field loss and deterioration of visual acuity. The patient with the missense mutation, however, was diagnosed with maculopathy. The IMPG2 gene encodes the interphotoreceptor matrix proteoglycan IMPG2, which is a constituent of the interphotoreceptor matrix. Our data therefore show that mutations in a structural component of the interphotoreceptor matrix can cause arRP. 相似文献