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41.
42.
López JA Bioley G Turtle CJ Pinzón-Charry A Ho CS Vuckovic S Crosbie G Gilleece M Jackson DC Munster D Hart DN 《Journal of immunological methods》2003,274(1-2):47-61
Dendritic cells (DC) for cancer immunotherapy protocols are generated most commonly by in vitro differentiation of monocytes with exogenous cytokines (Mo-DC). However, Mo-DC differ in their molecular phenotype and function from blood DC (BDC). Clinical isolation of BDC has been limited to the use of density gradients, which result in low yields of variable purity. We have developed a DC enrichment platform, which uses the CMRF-44 (IgM) or CMRF-56 (IgG) monoclonal antibodies (mAb) to select BDC that express these antigens after a short overnight incubation. After culture of peripheral blood mononuclear cells (PBMC) in autologous/AB serum, biotinylated CMRF-44 was used to select DC in a single step immuno-magnetic bead procedure; this produced populations containing up to 99% CMRF-44(+) cells, including up to 67% CMRF-44(+) CD14(-) CD19(-) DC, from an initial starting population of approximately 0.5%. We observed consistent differences in the purities obtained from individual donors with a mean of 54% CMRF-44(+) cells (range 19-99%). Similar results were obtained using biotinylated CMRF-56 mAb, an antibody identifying a comparable population in cultured PBMC. We recovered an average of 54% and 66% of the available BDC in separations performed with the CMRF-44 and CMRF-56 mAb, respectively. The reproducibility of the procedure and the ability to perform it in a closed sterile system makes it suitable for clinical use. Larger scale preparations starting from apheresis derived PBMC will produce sufficient BDC for immunotherapy protocols. The purified BDC elicited strong allogeneic mixed leukocyte reactions and HLA classes II- and I-restricted antigen-specific primary immune responses. 相似文献
43.
A further analysis of 1152 hospital autopsies provides data on inaccuracies of specific diagnoses; there are many examples of overdiagnosis and underdiagnosis. All were encountered in a routine hospital autopsy service and their frequency confirms the importance of the hospital autopsy in medical audit. A knowledge of the misdiagnoses which recur frequently could provide guidance in the selection of cases for autopsy. 相似文献
44.
Fein AJ Plotnikoff RC Wild TC Spence JC 《International journal of behavioral medicine》2004,11(3):135-142
The examination of physical environments to explain and promote physical activity is an important yet under-investigated area
of research inquiry. This study explored relationships between the perceived availability of physical environmental resources
and the perceived importance of these resources in relation to physical activity levels amongst youth. A self-report questionnaire
was completed by 610 students (mean age = 15.5 years old; 62% female participants) from four high schools (grades 9-12) in
rural Alberta, Canada. Perceived physical environment constructs explained 5% of the variance in physical activity, with home,
neighborhood, and school as significant domains. Perceived importance constructs explained 8% of the variance in physical
activity with school context showing the only significant relationship with physical activity. A hierarchical regression analysis
entered sex, grade, self-efficacy, peer, family and physical education teacher relationships, as the first block and eight
environmental constructs as the second block. The first block variables accounted for 22% of the variance and environmental
constructs accounted for an added 4% of the variance in physical activity. Perceived importance of the school environment
was the only environment variable significantly associated with physical activity (β = .14; p < .05) after taking into account
the impact of these traditional predictors. These findings reinforce the need to provide and support school physical environments
related to physical activity. 相似文献
45.
Swartz MJ Batra SK Varshney GC Hollingsworth MA Yeo CJ Cameron JL Wilentz RE Hruban RH Argani P 《American journal of clinical pathology》2002,117(5):791-796
Pancreatic adenocarcinoma is believed to develop from histologically identifiable intraductal lesions known as pancreatic intraepithelial neoplasias (PanINs) that undergo a series of architectural, cytologic, and genetic changes, a progression model similar to the adenoma-carcinoma sequence in the colon. The apomucin MUC4 has been implicated in invasive pancreatic adenocarcinoma. MUC4 expression is not detectable at the RNA level in normal pancreas but is detectable at high levels in invasive pancreatic adenocarcinoma. We documented the pattern of expression of MUC4 in PanINs by studying a series of 71 PanIN lesions immunohistochemically using a new monoclonal antibody to MUC4. Five (17%) of 30 PanIN-1 lesions, 10 (36%) of 28 PanIN-2 lesions, 11 (85%) of 13 PanIN-3 lesions, and 25 (89%) of 28 invasive adenocarcinomas labeled with the MUC4 antibody used in the study. In addition, afew nonneoplastic lesions labeled with the MUC4 antibody, including reactive ducts in chronic pancreatitis, atrophic ducts filled with inspissated secretions, and ducts showing squamous metaplasia. Our data help establish the patterns of MUC4 expression in neoplastic precursors in the pancreas and add further support to the progression model for pancreatic adenocarcinoma. 相似文献
46.
Bell CJ Wallace JL 《BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy》1997,7(4):273-284
Infiltration of leucocytes into the mucosa is a hallmark feature of a number of inflammatory bowel disorders, most notably Crohn's disease and ulcerative colitis. The interactions between circulating leucocytes and the vascular endothelium that permit leucocyte migration to a site of injury or infection are mediated via a variety of adhesion molecules. There is now ample evidence for alterations in adhesion molecule expression and function in inflammatory bowel disorders. This raises the possibility that adhesion molecules could be targets for novel therapies. Indeed, many existing anti-inflammatory drugs are capable of modulating adhesion molecule expression or function. Moreover, intensive research is under way to develop more selective and effective modulators of adhesion molecules, in the hope that they will be useful for treating various inflammatory disorders. 相似文献
47.
Two types of neutralisation or blocking test using human anti-HBs are described for the confirmation of positive results obtained by immunoradiometric screening for HBSAg. 相似文献
48.
Laforin preferentially binds the neurotoxic starch-like polyglucosans, which form in its absence in progressive myoclonus epilepsy 总被引:4,自引:0,他引:4
Chan EM Ackerley CA Lohi H Ianzano L Cortez MA Shannon P Scherer SW Minassian BA 《Human molecular genetics》2004,13(11):1117-1129
Lafora disease (LD) is a fatal and the most common form of adolescent-onset progressive epilepsy. Fulminant endoplasmic reticulum (ER)-associated depositions of starch-like long-stranded, poorly branched glycogen molecules [known as polyglucosans, which accumulate to form Lafora bodies (LBs)] are seen in neuronal perikarya and dendrites, liver, skeletal muscle and heart. The disease is caused by loss of function of the laforin dual-specificity phosphatase or the malin E3 ubiquitin ligase. Towards understanding the pathogenesis of polyglucosans in LD, we generated a transgenic mouse overexpressing inactivated laforin to trap normal laforin's unknown substrate. The trap was successful and LBs formed in liver, muscle, neuronal perikarya and dendrites. Using immunogold electron microscopy, we show that laforin is found in close proximity to the ER surrounding the polyglucosan accumulations. In neurons, it compartmentalizes to perikaryon and dendrites and not to axons. Importantly, it binds polyglucosans, establishing for the first time a direct association between the disease-defining storage product and disease protein. It preferentially binds polyglucosans over glycogen in vivo and starch over glycogen in vitro, suggesting that laforin's role begins after the appearance of polyglucosans and that the laforin pathway is involved in monitoring for and then preventing the formation of polyglucosans. In addition, we show that the laforin interacting protein, EPM2AIP1, also localizes on the polyglucosan masses, and we confirm laforin's intense binding to LBs in human LD biopsy material. 相似文献
49.
Congenital mesoblastic nephroma: possible prognostic and management value of assessing DNA content. 总被引:1,自引:0,他引:1 下载免费PDF全文
J C Barrantes C Toyn K R Muir S E Parkes F Raafat A H Cameron H B Marsden J R Mann 《Journal of clinical pathology》1991,44(4):317-320
The case records and pathology of all children with kidney tumours treated in the West Midlands Health Authority Region (WMHAR) from 1957 to 1986 were reviewed. The histology was reviewed by a panel of three paediatric pathologists. Thirteen (6%) out of 211 cases were considered to have congenital mesoblastic nephroma (CMN). Nine were of the conventional type, three of the atypical cellular type, and one mixed. DNA ploidy was investigated and showed two of the tumours to be aneuploid and nine diploid (tissue was not available in the two other cases). The two aneuploid tumours were of atypical cellular and mixed histology, respectively; the diploid tumours were of the conventional type in eight cases and atypical cellular in one. The atypical cellular type has been reported to behave more aggressively, but the benefit of additional treatment after surgery to prevent recurrence remains unclear. Measurement of DNA content by flow cytometry, together with histological subclassification, may be useful in selecting patients who will benefit from further treatment after surgery. 相似文献
50.
Telfer JF; Thomson AJ; Cameron IT; Greer IA; Norman JE 《Human reproduction (Oxford, England)》1997,12(10):2306-2312
Superoxide, an agent which attenuates the half-life of nitric oxide, is
metabolized and synthesized by superoxide dismutase (SOD) and xanthine
oxidase, respectively. Over the last few years much work has focused on the
role of nitric oxide in human parturition. The aim of this study was to
determine whether the onset of human parturition is associated with a
change in the expression of copper/zinc superoxide dismutase (Cu/Zn SOD),
manganese superoxide dismutase (Mn SOD) or xanthine oxidase within the
uterus. Samples of myometrium, placenta, decidua and fetal membranes were
obtained from women before and after the onset of labour at term.
Immunocytochemistry was used to localize Cu/Zn SOD, Mn SOD and xanthine
oxidase and measure SOD enzyme activity. Cu/Zn and Mn SOD-like
immunoreactivity was detected in syncytiotrophoblast cells, villous stromal
cells and endothelial cells of blood vessels in the placenta. In the
myometrium Cu/Zn and Mn SOD were localized to myocytes and endothelial
cells and to some vascular smooth muscle cells. In the fetal membranes we
observed staining for Cu/Zn SOD and Mn SOD in the amnion, chorion,
extravillous trophoblast and decidua. There was no difference in SOD enzyme
activity or staining intensity for SOD between different cell types before
and during labour. Xanthine oxidase immunoreactivity was identified in each
of the tissues examined and again there was no difference in immunostaining
in tissues obtained from women delivered before or after the onset of
labour. These results show that the pregnant uterus is capable of both
synthesizing and degrading superoxide and suggest that superoxide dismutase
and xanthine oxidase may play a role in the maintenance of uterine
quiescence during pregnancy, but not in the initiation of parturition.
相似文献