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51.
T. Iwanaga †‡ A. McEuen† A. F. Walls† J. B. Clough† T. P. Keith§ S. Rorke† S. J. Barton† S. T. Holgate† J. W. Holloway † 《Clinical and experimental allergy》2004,34(7):1037-1042
BACKGROUND: Mast cell chymase has the potential to be an important mediator of inflammation and remodelling in the asthmatic lung. Previous studies have examined association between promoter polymorphism of the chymase gene (CMA1) and allergic phenotypes but the significance of this polymorphism is unclear. We have examined association of a CMA1 variant in relation to asthma in a large UK Caucasian family cohort. METHODS: A polymorphism of the CMA1 gene promoter (-1903G/A) was genotyped in 341 asthmatic families and in 184 non-asthmatic adults recruited from the UK PCR-RFLP based genotyping. Association with asthma diagnosis, atopy, specific and total IgE, and atopy and asthma severity was examined. RESULTS: Case-control studies did not reveal a significant difference in allele frequency between asthmatics and controls. A significant association was found between CMA1 genotypes and total IgE levels in subjects with self-reported eczema that remained significant after correction for multiple testing (median total serum IgE GG 297 kU/L, GA 144 kU/L, AA 48.4 kU/L, Pc=0.0032). CONCLUSION: These data suggest that CMA1 promoter polymorphism does not contribute to asthma susceptibility or severity but may be involved in regulating IgE levels in patients with eczema. 相似文献
52.
S. Doğru-Abbasoğlu G. Aykaç-Toker H. A. Hanagasi H. Gürvit M. Emre M. Uysal 《Neurological sciences》2007,28(1):31-34
Abstract Alzheimer's disease (AD) is defined pathologically by the presence of β-amyloid plaques, neurofibrillary tangles and extensive
neuronal loss. Evidence indicates that increased DNA damage may contribute to neuronal loss in AD. Recently, it has been shown
that in AD neurons have a reduced capacity for some types of DNA repair. Polymorphisms in DNA repair genes may be associated
with differences in repair efficiency of DNA damage. Variants of several DNA repair genes, including the base excision repair
gene XRCC1, have been described previously. We hypothesised that Arg194Trp polymorphism of XRCC1 gene may contribute to genetic susceptibility for AD. In order to test this hypothesis, we investigated
Arg194Trp polymorphism at the XRCC1 gene in the DNA samples of 98 patients with AD and 95 healthy subjects. The frequency of the Trp allele was more pronounced among cases (11.2%) compared with controls (5.8%). On combining the homozygous and heterozygous
variants of each codon, the variants seemed to be at twofold risk of AD, although the risk estimates were not statistically
significant (OR=1.95, 95% CI 0.88–4.34, p=0.09). In addition, the 194Trp allele revealed a borderline significance (OR=2.05, 95% CI 0.96–4.37, p=0.056). According to our results, it may be speculated that the polymorphic variants of XRCC1 codon 194 have a role in the
development of AD. 相似文献
53.
James A. Case Bai Ling Hsu Timothy M. Bateman S. James Cullom 《Journal of nuclear cardiology》2007,14(3):324-333
Background High-quality attenuation maps are critical for attenuation correction of myocardial perfusion single photon emission computed
tomography studies. The filtered backprojection (FBP) approach can introduce errors, especially with low-count transmission
data. We present a new method for attenuation map reconstruction and examine its performance in phantom and patient data.
Methods and Results The Bayesian iterative transmission gradient algorithm incorporates a spatially varying gamma prior function that preferentially
weights estimated attenuation coefficients toward the soft-tissue value while allowing data-driven solutions for lung and
bone regions. The performance with attenuation-corrected technetium 99m sestamibi clinical images was evaluated in phantom
studies and in 50 low-likelihood patients grouped by body mass index (BMI). The algorithm converged in 15 iterations in the
phantom studies. For the clinical studies, soft-tissue estimates had significantly greater uniformity of mediastinal coefficients
(mean SD, 0.005 cm−1 vs 0.011 cm−1; P<.0001). The accuracy and uniformity of the Bayesian iterative transmission gradient algorithm were independent of BMI, whereas
both declined at higher BMI values with FBP. Attenuation-corrected perfusion images showed improvement in myocardial wall
variability (4.8% to 4.1%, P=.02) for all BMI groups with the new method compared with FBP.
Conclusion This new method for attenuation map reconstruction provides rapidly converging and accurate attenuation maps over a wide spectrum
of patient BMI values and significantly improves attenuation-corrected perfusion images. 相似文献
54.
B. Berghöfer T. Frommer I. R. König† A. Ziegler† T. Chakraborty‡ G. Bein H. Hackstein 《Clinical and experimental allergy》2005,35(9):1147-1154
BACKGROUND: Toll-like receptor 9 (TLR9) is a pattern-recognition receptor that detects unmethylated CpG motifs prevalent in bacterial and viral DNA. TLR9 stimulation is a key event after bacterial infection, triggering innate immunity and T-helper type 1 skewed adaptive immunity. Synthetic CpG-oligodeoxynucleotides (CpG-ODNs) represent a promising and novel class of immune adjuvants for allergy treatment, vaccination, and cancer therapy. However, common functional TLR9 gene variants could interfere with the clinical utilization of CpG-ODN in immunotherapy. Recently, a possible association of TLR9 polymorphism C-1237T with asthma has been reported. OBJECTIVE: The aim of the present study was to investigate whether TLR9 polymorphisms or haplotypes have functional relevance and are associated with atopy. METHODS: We genotyped five common TLR9 single-nucleotide polymorphisms (SNPs) in promoter, exon, and intron regions of the gene in 527 healthy blood donors, and estimated four common haplotypes. The total IgE and specific IgE levels against the most common aeroallergens were measured (n=303). IFN-alpha production by plasmacytoid dendritic cells (pDCs) was analysed after stimulation with TLR9 ligand CpG-ODN (n=220). RESULTS: No significant influence of common TLR9 polymorphisms and haplotypes on the total and specific IgE levels was found. Functional analysis of CpG-ODN-induced IFN-alpha did not indicate a significant role for common TLR9 gene polymorphisms in TLR9 function. CONCLUSION: We conclude that common genetic differences in the TLR9 gene exert no major influence on allergy susceptibility, and are unlikely to have on impact on clinical application of CpG-ODNs. 相似文献
55.
Cytokines have a central role in multiple sclerosis (MS) pathogenesis and may contribute to the aetiology of MS. A polymorphism in the IFNA17 gene with an allele carrying a pre-mature stop codon has been suggested to convey a 26-fold increased risk for MS. We investigated the possible association between this polymorphism and MS using population-based samples from a genetically well-characterized population. The IFNA17 gene variant was found in 2.8% of 327 MS cases and 3.3% of 698 referents ( P = 0.64). Thus, our study does not support an association between the IFNA17 allele and risk for MS. 相似文献
56.
57.
58.
纤溶酶原激活剂抑制物-1及其基因多态性与急性心肌梗死的相关性研究 总被引:2,自引:0,他引:2
目的:研究纤溶酶原激活剂抑制物-1(PAI-1)活性及其等位基因多态性与急性心肌梗死(AMI)之间的关系,从基因水平揭示AMI发病的危险因素。方法:AMI组55例、对照组48例健康者分别应用特异性寡核苷酸点膜杂交技术,进行PAI-1启动子区4G/5G多态性分析,用发色底物法测定血浆PAI-1活性。结果:AMI组和对照组中4G/4G基因型的血浆PAI-1活性水平最高,与4G/5G基因型、5G/5G基因型比较有显著性差异(P<0.01)。AMI组中4G/4G纯合子基因型频率明显高于对照组(P<0.05)。结论:血浆PAI-1活性增高是AMI发病的危险因素之一,4G/4G纯合子基因型是AMI发病的危险基因型。 相似文献
59.
The differential effects of the pyrethroid tetramethrin on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) single sodium channel currents in rat dorsal root ganglion (DRG) neurons were investigated using the outside-out configuration of patch-clamp technique. Channel conductances were 10.7 and 6.3 pS for TTX-S and TTX-R sodium channels, respectively, at a room temperature of 24–26°C. The single-channel current of TTX-S sodium channels at the test potential of −30 mV was −1.27 ± 0.25 pA, and was not changed after exposure to 10 μM tetramethrin (−1.28 ± 0.23 pA). The open time histogram of TTX-S single-channel currents could be fitted by a single exponential function with a time constant of 1.27 ms. After exposure to 10 μM tetramethrin, the open time histogram could be fitted by the sum of two exponential functions with time constants of 1.36 ms (τfast) and 5.73 ms (τlow). The percentage of contribution of each component to the population was 62% for the fast component representing the normal channels and 38% for the slow component representing the tetramethrin modified channels. The amplitudc of TTX-R single-channel currents was slightly changed from −0.72 ± 0.14 to −0.83 ± 0.07 pA by 10 μM tetramethrin. The open time histogram of TTX-R single-channel currents could be fitted by a single exponential function with a time constant of 1.92 ms. In the presence of 10 μM tetramethrin, the open time histogram could be fitted by the sum of two exponential functions with time constants of 2.07 ms (τfast) and 9.75 ms (τslow). The percentage of contribution of each component was 15% for the fast, unmodified component and 85% for the slow, modified component. Differential effects of tetramethrin on the open time distribution of single sodium channel currents explains the differential sensitivity of TTX-S and TTX-R sodium channels. 相似文献
60.