全文获取类型
收费全文 | 1571篇 |
免费 | 95篇 |
国内免费 | 2篇 |
专业分类
耳鼻咽喉 | 18篇 |
儿科学 | 34篇 |
妇产科学 | 34篇 |
基础医学 | 263篇 |
口腔科学 | 100篇 |
临床医学 | 104篇 |
内科学 | 300篇 |
皮肤病学 | 19篇 |
神经病学 | 190篇 |
特种医学 | 57篇 |
外科学 | 212篇 |
综合类 | 2篇 |
一般理论 | 1篇 |
预防医学 | 99篇 |
眼科学 | 26篇 |
药学 | 93篇 |
中国医学 | 8篇 |
肿瘤学 | 108篇 |
出版年
2024年 | 3篇 |
2023年 | 14篇 |
2022年 | 36篇 |
2021年 | 65篇 |
2020年 | 35篇 |
2019年 | 67篇 |
2018年 | 66篇 |
2017年 | 51篇 |
2016年 | 52篇 |
2015年 | 65篇 |
2014年 | 63篇 |
2013年 | 107篇 |
2012年 | 164篇 |
2011年 | 174篇 |
2010年 | 78篇 |
2009年 | 89篇 |
2008年 | 105篇 |
2007年 | 90篇 |
2006年 | 72篇 |
2005年 | 76篇 |
2004年 | 49篇 |
2003年 | 50篇 |
2002年 | 27篇 |
2001年 | 16篇 |
2000年 | 4篇 |
1999年 | 8篇 |
1998年 | 4篇 |
1997年 | 5篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 5篇 |
1991年 | 1篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 4篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1978年 | 2篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1962年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有1668条查询结果,搜索用时 15 毫秒
21.
22.
Csepregi A Röcken C Hoffmann J Gu P Saliger S Müller O Schneider-Stock R Kutzner N Roessner A Malfertheiner P Ebert MP 《Journal of cancer research and clinical oncology》2008,134(5):579-589
Purpose We investigated the impact of promoter methylation on APC protein expression in patients with hepatocellular carcinoma (HCC).
Materials and methods 50 patients [HCC (n=19), liver metastasis (n=19), cholangiocellular cancer (n=7), and benign liver tumors (n=5)] were studied
for methylation using Methylight analysis. APC mutation was investigated by protein truncation test and direct sequencing
of genomic DNA. The protein expression was evaluated by immunohistochemistry and Western blot analysis.
Results The APC promoter was hypermethylated in 81.8% of non-cancerous liver tissue samples. All HCC samples and ten patients with
liver metastasis (52.6%) exhibited APC promoter methylation. The degree of methylation was significantly higher in samples
from HCC compared to the non-cancerous liver tissue samples (63.1% vs. 24.98%; p=0.001). The level of APC protein expression
was significantly reduced in HCC samples compared to that of the corresponding non-tumor liver tissue (p<0.05).
Conclusions Promoter methylation of the APC gene seems to be of significance in hepatocarcinogenesis and results in reduced protein expression
in HCC. Interestingly, APC promoter methylation is also present in the vast majority of non-cancerous liver tissue whose (patho)physiological
function remains unresolved. 相似文献
23.
Bernt Popp Svein I St?ve Sabine Endele Line M Myklebust Juliane Hoyer Heinrich Sticht Silvia Azzarello-Burri Anita Rauch Thomas Arnesen André Reis 《European journal of human genetics : EJHG》2015,23(5):602-609
Recent studies revealed the power of whole-exome sequencing to identify mutations in sporadic cases with non-syndromic intellectual disability. We now identified de novo missense variants in NAA10 in two unrelated individuals, a boy and a girl, with severe global developmental delay but without any major dysmorphism by trio whole-exome sequencing. Both de novo variants were predicted to be deleterious, and we excluded other variants in this gene. This X-linked gene encodes N-alpha-acetyltransferase 10, the catalytic subunit of the NatA complex involved in multiple cellular processes. A single hypomorphic missense variant p.(Ser37Pro) was previously associated with Ogden syndrome in eight affected males from two different families. This rare disorder is characterized by a highly recognizable phenotype, global developmental delay and results in death during infancy. In an attempt to explain the discrepant phenotype, we used in vitro N-terminal acetylation assays which suggested that the severity of the phenotype correlates with the remaining catalytic activity. The variant in the Ogden syndrome patients exhibited a lower activity than the one seen in the boy with intellectual disability, while the variant in the girl was the most severe exhibiting only residual activity in the acetylation assays used. We propose that N-terminal acetyltransferase deficiency is clinically heterogeneous with the overall catalytic activity determining the phenotypic severity. 相似文献
24.
Michael Zech MD Robert Jech MD PhD Sylvia Boesch MD Matej Škorvánek MD PhD Ján Necpál MD Jana Švantnerová MD Matias Wagner MD Ariane Sadr-Nabavi PhD Felix Distelmaier MD Martin Krenn MD PhD Tereza Serranová MD PhD Irena Rektorová MD PhD Petra Havránková MD PhD Alexandra Mosejová MD Iva Příhodová MD PhD Jana Šarláková MD Kristína Kulcsarová MD Olga Ulmanová MD PhD Karel Bechyně MD Miriam Ostrozovičová MD Vladimír Haň MD PhD Joaquim Ribeiro Ventosa MD Theresa Brunet MD Riccardo Berutti PhD Mohammad Shariati MD Ali Shoeibi MD Susanne A. Schneider MD Alice Kuster MD Matthias Baumann MD David Weise MD Friederike Wilbert MD Wibke G. Janzarik MD Matthias Eckenweiler MD Volker Mall MD Bernhard Haslinger MD Steffen Berweck MD Juliane Winkelmann MD Konrad Oexle MD 《Movement disorders》2021,36(8):1959-1964
25.
26.
Fabian Brunk Andreas Moritz Annika Nelde Tatjana Bilich Nicolas Casadei Sabine A. K. Fraschka Jonas S. Heitmann Sebastian Hörber Andreas Peter Hans-Georg Rammensee Harpreet Singh Juliane Walz Dominik Maurer Claudia Wagner 《European journal of immunology》2021,51(11):2651-2664
Both B cells and T cells are involved in an effective immune response to SARS-CoV-2, the disease-causing virus of COVID-19. While B cells—with the indispensable help of CD4+ T cells—are essential to generate neutralizing antibodies, T cells on their own have been recognized as another major player in effective anti-SARS-CoV-2 immunity. In this report, we provide insights into the characteristics of individual HLA-A*02:01- and HLA-A*24:02-restricted SARS-CoV-2-reactive TCRs, isolated from convalescent COVID-19 patients. We observed that SARS-CoV-2-reactive T-cell populations were clearly detectable in convalescent samples and that TCRs isolated from these T cell clones were highly functional upon ectopic re-expression. The SARS-CoV-2-reactive TCRs described in this report mediated potent TCR signaling in reporter assays with low nanomolar EC50 values. We further demonstrate that these SARS-CoV-2-reactive TCRs conferred powerful T-cell effector function to primary CD8+ T cells as evident by a robust anti-SARS-CoV-2 IFN-γ response and in vitro cytotoxicity. We also provide an example of a long-lasting anti-SARS-CoV-2 memory response by reisolation of one of the retrieved TCRs 5 months after initial sampling. Taken together, these findings contribute to a better understanding of anti-SARS-CoV-2 T-cell immunity and may contribute to paving the way toward immunotherapeutics approaches targeting SARS-CoV-2. 相似文献
27.
de França Juliane Santos de Sales-Neto José Marreiro Carvalho Deyse Cristina Madruga de Almeida Lima Éssia Olegário Tayná Rodrigues Mendes Rhuan Karlos Santos Lima-Junior Claudio Gabriel de Almeida Vasconcellos Mário Luiz Araújo Rodrigues-Mascarenhas Sandra 《Inflammation》2021,44(3):899-907
Inflammation - Morita-Baylis-Hillman adducts (MBHA) are synthetic molecules with several biological actions already described in the literature. It has been previously described that adduct... 相似文献
28.
Brenda Stefany dos Santos Braga Dário Lisboa Fernandes-Neto Leonardo Conceição Teixeira Juliane da Silva Costa Maria Auxiliadora Pantoja Ferreira Verônica Regina Oliveira-Bahia José Ribamar Felipe Marques Diva Anelie de Araújo Guimarães 《Anatomical record (Hoboken, N.J. : 2007)》2021,304(6):1280-1293
The morphological study of limbs is important for the understanding of tetrapod biology, where it can be applied to taxonomy and phylogeny, as well ecology and behavior. In this study area, osteogenesis is a subject in Kinosternidae, which has been little researched. The main aim of this study was to characterize the skeletogenesis of Kinosternon scorpioides limbs. Samples were histologically processed, and the embryos were cleared with potassium hydroxide and stained with alcian blue and alizarin red. It was observed that the limbs arose in embryonic Stage 10 as mesenchymal condensate cells. The first stylopodium chondrification centers were noted at Stage 14. Zeugopodium chondrification centers appeared at Stage 15; carpal, metacarpal, tarsal, and metatarsal regions were observed at Stage 16, and the cartilage molds of all bones limbs were present at Stage 18. Ossification began in the humerus and femur at Stage 20, and continued into the radius, ulna, tibia, and fibula bones. By Stage 23, it was already effectively directed toward the bone epiphyses in both limbs. At Stage 26 and hatching, only articular cartilages remained, and in the majority of samples the carpal region showed no affinity for alcian blue or alizarin red staining. This study acts as an indicative parameter of the taxon's normal development and can contribute to the phylogenetic understanding of this group. 相似文献
29.
Rainer Haak Juliane Siegner Dirk Ziebolz Uwe Blunck Sabine Fischer Jan Hajtó Roland Frankenberger Felix Krause Hartmut Schneider 《Dental materials》2021,37(3):423-431
ObjectivesIn-vitro evaluation of the influence of preparation design and thickness of ceramic veneers on the interfacial bond using optical coherence tomography (OCT).MethodsSixty-four central incisors were randomly assigned to four preparation designs differing from no to complete dentine exposure (n = 16 each): non-prep (NP), minimal-invasive (MI, no dentine exposure), semi-invasive (SI, 50% dentine) and invasive (I, 100% dentine). Ceramic veneers (IPS InLine Veneer) of two thicknesses (0.2?0.5 mm (T1) and > 0.5–1.2 mm (T2)) were etched, silanized, and adhesively luted (Optibond FL, Variolink Veneer). After water storage (37 °C, 21d), thermocycling (2000 cycles, 5°-55 °C), and mechanical loading (2 + 1 million cycles, 50 + 100 N) specimens were imaged by spectral-domain OCT (Telesto II, Thorlabs). Adhesive defects at the ceramic-composite and tooth-composite interfaces were quantified on 35 equidistantly distributed OCT B-scans (length, %). Statistical differences were verified with Wilcoxon-/Mann-Whitney-U-test (α = 0.05).ResultsAdhesive defects appeared in all groups at both interfaces, albeit to differing extents (0.1 – 31.7%). NP and MI veneers showed no significant differences at the interfaces (pi > 0.05). In groups, SI and I, significantly more adhesive defects appeared at the tooth-composite compared to the veneer-composite interface (pi ≤ 0.039). The following preparation designs and veneer thicknesses showed differences (pi ≤ 0.021): Veneer-composite: NP-T1 < I-T1, MI-T1 < I-T1, I-T1 > I-T2; Tooth-composite: NP-T1 < SI-T1, NP-T1 < I-T1, NP-T2 > MI-T2, MI-T1 < SI-T1, MI-T1 < I-T1, SI-T1 < I-T1, MI-T2 < SI-T2, MI-T2 < I-T2.SignificanceThe interface adhesion of ceramic veneers was influenced by the preparation design and the veneer thickness. A ceramic thickness of at least 0.5 mm and a preparation without exposing dentine is advantageous for the interfacial bond. 相似文献
30.
Konrad Oexle Barbara Schormair Janina S Ried Darina Czamara Katharina Heim Birgit Frauscher Birgit H?gl Claudia Trenkwalder G Martin Fiedler Joachim Thiery Peter Lichtner Holger Prokisch Michael Specht Bertram Müller-Myhsok Angela D?ring Christian Gieger Annette Peters H-Erich Wichmann Thomas Meitinger Juliane Winkelmann 《European journal of human genetics : EJHG》2013,21(4):410-414
Restless legs syndrome (RLS) is a common multifactorial disease. Some genetic risk factors have been identified. RLS susceptibility also has been related to iron. We therefore asked whether known iron-related genes are candidates for association with RLS and, vice versa, whether known RLS-associated loci influence iron parameters in serum. RLS/control samples (n=954/1814 in the discovery step, 735/736 in replication 1, and 736/735 in replication 2) were tested for association with SNPs located within 4 Mb intervals surrounding each gene from a list of 111 iron-related genes using a discovery threshold of P=5 × 10−4. Two population cohorts (KORA F3 and F4 with together n=3447) were tested for association of six known RLS loci with iron, ferritin, transferrin, transferrin-saturation, and soluble transferrin receptor. Results were negative. None of the candidate SNPs at the iron-related gene loci was confirmed significantly. An intronic SNP, rs2576036, of KATNAL2 at 18q21.1 was significant in the first (P=0.00085) but not in the second replication step (joint nominal P-value=0.044). Especially, rs1800652 (C282Y) in the HFE gene did not associate with RLS. Moreover, SNPs at the known RLS loci did not significantly affect serum iron parameters in the KORA cohorts. In conclusion, the correlation between RLS and iron parameters in serum may be weaker than assumed. Moreover, in a general power analysis, we show that genetic effects are diluted if they are transmitted via an intermediate trait to an end-phenotype. Sample size formulas are provided for small effect sizes. 相似文献