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1.
BMP-2 gene polymorphisms and osteoporosis: the Rotterdam Study. 总被引:7,自引:0,他引:7
Marco Medici Joyce Bj van Meurs Fernando Rivadeneira HongYan Zhao Pascal P Arp Albert Hofman Huibert Ap Pols André G Uitterlinden 《Journal of bone and mineral research》2006,21(6):845-854
After reported associations of variations in the BMP-2 gene with osteoporosis in small populations, we studied the association of the BMP-2 gene polymorphisms Ser37Ala and Arg190Ser with osteoporosis in 6353 men and women from the Rotterdam Study. We did not observe an association of these variants with BMD, bone loss, hip structural analysis parameters, and fracture risk. INTRODUCTION: Bone morphogenetic protein 2 (BMP-2) plays a role in osteoblast differentiation. BMP-2 gene variation has previously been associated with osteoporosis in various small populations, but current evidence remains inconclusive about the exact association with osteoporosis. Therefore, we studied the association of two polymorphisms located in the BMP-2 gene (Ser37Ala and Arg190Ser) and haplotypes defined by these polymorphisms with BMD, rates of bone loss, parameters of hip structural analysis (HSA), and fractures in the Rotterdam Study, a large prospective cohort study of diseases in the elderly. MATERIALS AND METHODS: Databases were searched for polymorphisms and haplotype blocks in the BMP-2 gene region. Allele frequencies for Ser37Ala and Arg190Ser were determined in 60 blacks and 110 Chinese from Coriell panels. Genotype data on Ser37Ala and Arg190Ser were available for 6353 individuals from the Rotterdam Study population. Haplotype alleles defined by Ser37Ala and Arg190Ser were inferred using PHASE software. Genotype and haplotype analyses for BMD (measured at the lumbar spine and femoral neck), bone loss per year (measured at the femoral neck), and HSA were performed using AN(C)OVA. Fractures were analyzed using a Cox proportional-hazards model and logistic regression. All outcomes were adjusted for age, height, and weight. RESULTS: Allele frequencies were 2.5% for Ala37 and 40.2% for Ser190, whereas haplotype allele frequencies were 57.28% (Ser37Arg190), 40.19% (Ser37Ser190), 2.50% (Ala37Arg190), and 0.02% (Ala37Ser190). For BMD, bone loss, HSA outcomes, and (incident) fractures, no differences could be seen between genotype and haplotype groups. Conclusions: In this large population-based cohort of Dutch whites, we conclude that the BMP-2 Ser37Ala and Arg190Ser polymorphisms or haplotypes thereof are not associated with parameters of osteoporosis. 相似文献
2.
D. M. Reid I. Mackay S. Wilkinson C. Miller D. G. Schuette J. Compston C. Cooper E. Duncan N. Galwey R. Keen B. Langdahl A. McLellan H. Pols A. Uitterlinden J. O’Riordan J. A. H. Wass S. H. Ralston S. T. Bennett 《Osteoporosis international》2006,17(1):125-132
Osteoporosis is a common disease with a strong genetic component characterized by reduced bone mass and an increased risk of fragility fractures. Bone mineral density (BMD) is the most important determinant of osteoporotic fracture risk, but the genes responsible for BMD regulation and fracture are incompletely defined. To enable multi-center studies to examine the genetic influences on BMD there is a requirement to standardize measurements across different manufacturers of bone densitometers, different versions of machines and different normative ranges. This paper describes a method developed to allow near-identical subjects with low age-adjusted BMD (based on Z-scores) to be recruited in 17 centers using 27 different densitometers. Cross-calibration was based on measurements using a European spine phantom circulated to all centers and measured ten times on each individual machine. From theses values an individual exponential curve, based on nominal versus observed BMD, was derived for each machine. As expected, there were large and significant variations in nominal BMD values, not only between scanners from different manufacturers but also between different versions of scanners from the same manufacturer. Hologic scanners tended to underestimate the nominal BMD, while Lunar scanners overestimated the value. Norland scanners gave mixed values over estimating BMD at the lower nominal value (0.5 g/cm2) while underestimating the value at the higher value (1.5 g/cm2). The validity of the exponential equations was tested using hip and spine measurements on 991 non-proband women from a familial osteoporosis study (FAMOS). After cross-calibration there was a considerable reduction in variation between machines. This observation, coupled with the absence of a similar reduction in variation attributable to a linear regression on age, demonstrated the validity of the cross-calibration approach. Use of the cross-calibration curves along with a standard normative range (in the case of this study, the Hologic normative range) allowed age-specific Z-scores to be used as an inclusion criterion in this genetic study, a method that will be useful for other trials where age-specific BMD inclusion criteria are required. 相似文献
3.
4.
AG Nettetal 《MedR Medizinrecht》2007,25(11):664-666
Abstrakt 1. Nimmt ein Patient einen ihm von seinem (Zahn-)Arzt einger?umten Exklusiv-Termin nicht wahr, obwohl er auf dessen Eigenschaft
ausdrücklich hingewiesen wurde, so hat er dem (Zahn-)Arzt den Behandlungsausfall abzüglich eines angemessenen Eigenanteils
des (Zahn-)Arztes zu ersetzen.
2. Die Ersatzpflicht tritt auch dann ein, wenn der Patient den Termin nicht in der in dem Behandlungsvertrag vorgesehenen
Frist absagt. Eine hierfür seitens des (Zahn-)Arztes bestimmte Frist von zwei Tagen vor Behandlungsbeginn stellt sich für
den Patienten grunds?tzlich auch nicht als unangemessene Benachteiligung i.S. des § 307 BGB dar.
3. Ein Anspruch des Arztes entf?llt auch bei nur mündlicher Vereinbarung nicht unter dem Gesichtspunkt des § 4 Abs. 5b BMV-Z,
denn diese Vorschrift ist teleologisch dahin zu reduzieren, dass nur zahn?rztliche Honoraransprüche aus erfolgten Behandlungen
schriftlich vereinbart werden müssen. Soweit es jedoch um einen vertraglichen Anspruch wegen einer Leistungsst?rung geht,
vermag das Schriftformerfordernis des § 4 Abs. 5b BMV-Z grunds?tzlich nicht einzugreifen. (Leits?tze des Bearbeiters) 相似文献
5.
6.
Early during rat thymus ontogeny, an important proportion of thymocytes
expresses IL-2R and contains IL-2 mRNA. To investigate the role of the
IL-2-IL-2R complex in rat T cell maturation, we supplied either recombinant
rat IL-2 or blocking anti-CD25 mAb to rat fetal thymus organ cultures
(FTOC) under several experimental conditions. The IL-2 treatment initially
stimulated the growth of thymocytes and, as a result, induced T cell
differentiation, but the continuous addition of IL-2 to rat FTOC, as well
as the anti-CD25 administration, resulted in cell number decrease and
inhibition of thymocyte maturation. These results indicate that immature
rat thymocytes bear functional high- affinity IL-2R and that IL-2 promotes
T cell differentiation as a consequence of its capacity to stimulate cell
proliferation. Modifications in TCR alpha beta repertoire and increased
numbers of NKR- P1+ cells, largely NK cells, were also observed in
IL-2-treated FTOC. Furthermore, IL-2-responsiveness of different thymocyte
subsets changed throughout thymic ontogeny. Immature CD4-CD8-cells
responded to IL-2 in two stages, early in thymus development and around
birth, in correlation with the maturation of two distinct waves of thymic
cell progenitors. Mature CD8+ thymocytes maximally responded to IL-2 around
birth, supporting a role for IL-2 in the increased proliferation of mature
thymocytes observed in vivo in the perinatal period. Taken together, these
findings support a role for IL-2 in rat T cell development.
相似文献
7.
Life expectancy in British Marfan syndrome populations 总被引:2,自引:0,他引:2
JR Gray AB Bridges RR West L. McLeish AG Stuart JCS Dean MEM Porteous M. Boxer SJ Davies 《Clinical genetics》1998,54(2):124-128
A total of 206 patients with Marfan syndrome were ascertained throughout genetic clinics in Wales and Scotland during the period 1970–1990. There were 45 deaths representing 22% of the cohort. Mean age at death was 45.3 ± 16.5 years. 50% median cumulative survival in the total cohort (n = 206) was 53 years for males and 72 years for females. Multivariate analysis confirmed severity as the best independent indicator of survival. These findings and survival curves will assist in the counselling of British families and individuals with Marfan syndrome. 相似文献
8.
B. Guigas J. E. de Leeuw van Weenen N. van Leeuwen A. M. Simonis‐Bik T. W. van Haeften G. Nijpels J. J. Houwing‐Duistermaat M. Beekman J. Deelen L. M. Havekes B. W. J. H. Penninx N. Vogelzangs E. van ‘t Riet A. Dehghan A. Hofman J. C. Witteman A. G. Uitterlinden N. Grarup T. Jørgensen D. R. Witte T. Lauritzen T. Hansen O. Pedersen J. Hottenga J. A. Romijn M. Diamant M. H. H. Kramer R. J. Heine G. Willemsen J. M. Dekker E. M. Eekhoff H. Pijl E. J. de Geus P. E. Slagboom L. M. ‘t Hart 《Diabetic medicine》2014,31(8):1001-1008
9.