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1.
Lara Feulner Hamed S. Najafabadi Simon Tanguay Janusz Rak Yasser Riazalhosseini 《Urologic oncology》2019,37(2):166-175
Background
Clear cell renal cell carcinoma (ccRCC) is known to occur across the adult lifetime traversing the spectrum of age-related organismal changes. Little is known as to how the aging process may affect the course of renal cell carcinoma (RCC) and the repertoire of genes involved.Methods
Using The Cancer Genome Atlas (n?=?436) and Cancer Genomics of the Kidney (n?=?89) datasets, we applied regression analysis to examine associations between patient age and gene expression profiles in ccRCC tumors and normal kidney tissues. Pathway enrichment analysis was performed to identify cellular process that is affected by aging in ccRCC. Moreover, connectivity mapping analysis was used to predict age-dependent response to drug treatments.Results
Our analysis revealed different age-dependent gene expression spectra in ccRCC and normal kidney tissues. These findings were significant and independently reproducible in both datasets examined. Age up-regulated genes, showing higher expression in older patients, were significantly enriched (false discovery rate <0.05) in normal tissues for pathways associated with immune response and extracellular matrix organization, whereas age up-regulated genes in tumors were enriched for metabolism and oxidation pathways. Strikingly, age down-regulated genes in normal cells were also enriched for metabolism and oxidation, while those in tumors were enriched for extracellular matrix organization. Further in silico analysis of potential drug targets predicted preferential efficacy of Phosphoinositide 3-kinase inhibitor or immunotherapy in association with age.Conclusion
We report on previously unrecognized associations between age and molecular underpinnings of RCC, including age-associated expression of genes implicated in RCC development or treatment. 相似文献2.
Background
Aromatic l-amino acid decarboxylase (AADC) deficiency (OMIM #608643) is a rare and severe disorder of biogenic amine synthesis caused by mutations in the DDC gene. The phenomenology of the movement disorder includes intermittent oculogyric crises and limb dystonia, generalized athetosis, and impaired voluntary movement.Objective
To identify clinical manifestations and DDC gene mutations in two Chinese mainland children who are siblings with AADC deficiency.Methods
We used targeted next-generation sequencing and quantitative polymerase chain reaction (qPCR) to reveal DDC mutations in these children.Results
Two DDC gene mutations were found: one missense mutation, c.1040G?>?A (p.Arg347Gln), is a reported mutation derived from the mother; the other mutation, a whole-exon 11 and 12 deletion, is a novel mutation derived from the father. The index patient and her brother both had poor sucking power and feeding difficulty at birth and episodes of oculogyric crises, truncal hypotonia, limb hypertonia, sleep disturbances, irritability, and motor delay. The siblings both died at 1?year and 10?months due to asphyxia and pneumonia during gaze and hypertonia episodes.Conclusion
This study identified a novel DDC gene deletion mutation in two siblings with AADC deficiency disease in the Chinese mainland population. 相似文献3.
4.
Objestive Systemic inflarmmation may be triggered by injury, hypothermia, ischemia-reperfusion and the contact of the blood with foreign body during cardiopulmonary bypass (CPB). To determine the application values of gene chip technique in the clinical practice and the study of cardiovascular stagery, as well as to provide clues to the study of inflammatory responess during CPB, microarry for gene expression profiles was used to identify the differences in the gene expression of myocardium between pre-and post- CPB. Methods Six adult patients who underwent CPB from March to May in 2003 were involved. Samples of right atrium were col- lected before and at immediate end of CPB. BD AtlasTM cDNA Expression Arrays was used to identify the differences in the gene ex- pression of cytokines. The results were compared with that of semi-quantative RT-PCR. Resellts The mean age of 6 patients (5 males and 1 female) was (32.67± 11.72) years. The baseline heart function was gradeⅡin 3 cases and grade Ⅲ in 3 other cases. The baseline left ventricular ejection fraction(LVEF)was (58.17±7.91)%. The mere duration was (91.67±43.88) minutes for CPB and was (58.67±43.46) minutes for aorta blocking. The minimum nasopharynx/rectal temperture was (29.37±1.90)℃/ (32.15±1.52)℃. Gene expression profiles of cytokines in the myocardium pre- and post-CPB were analysed successfully. The ex- pression of IL-6, IFN-γ,Wnt5a, TNFRSF1B, a member of tumor necrosis factor receptor superfamily, PIGF and MFNG in the myo- cardium were unpregulated after CPB. Conclusion Microarray technique is applicable in the study of cytokines changes dying CPB. cDNA microarray identified pleliminarily the differences in the gene expression between pre- and post-CPB. These genes may be in- valved in inflammation and other psthophysiological responses incuced by CPB. The myocardiym is probably one of the major sources of cytokines during CPB. Further study may be helpful in understanding the llngthe development of inflammation during CPB, and eventually, reducing the post-operative complications. 相似文献
5.
CYP2E1 and ALDH2 Genotypes and Alcohol Dependence in Japanese 总被引:2,自引:0,他引:2
Kazuhiko Iwahashi Yoshinori Matsuo Hiroshi Suwaki Kazuhiko Nakamura Yoshiyuki Ichikawa 《Alcoholism, clinical and experimental research》1995,19(3):564-566
The genotypes of the CYP2E1 and ALDH2 loci of alcoholic (alcohol dependence) and nonalcoholic (healthy) Japanese were investigated to examine the relationship between the polymorphism of CYP2E1 (C1 /C2 ) and ALDH2 ( ALDH2*1/ALDH2*2 ), and the susceptibility to alcoholism. There was no significant difference in C2 gene frequency between alcoholics (0.19) and nonalcoholics (controls) (0.20), whereas there was a significant difference in ALDH2 allele frequency, suggesting that, in Japanese, the C2 genotype of CYP2E1 may have nothing to do with the risk of developing alcohol dependence. However, the ALDH2*1 allele may influence drinking behavior and the development of alcohol dependence. Furthermore, racial interethnic differences in the frequency of the mutated allele of the CYP2E1 gene (CJ were found, like the ALDH2 gene. Japanese healthy controls showed a significantly higher frequency of the C2 allele than did Swedish healthy controls (0.05; reported by Persson et al., FEBS Lett. 319:207-211,1993). 相似文献
6.
由于软骨组织内无血管,因此其损伤后仅靠其自身来修复是非常有限的.有研究表明,很多细胞因子具有促进软骨形成及软骨样组织修复的功能.由细胞介导的相关基因于损伤部位分泌这些细胞因子促进软骨修复被认为足最理想的治疗方法.基因治疗正是在这一基础上发展起来的一种治疗技术,近年来取得了快速的发展.就近期软骨损伤的基因治疗进展进行综述. 相似文献
7.
Marie-Paule Roth Hlne Coppin Patrick Descoins Jean-Bernard Ruidavets Anne Cambon-Thomsen Michel Clanet 《Journal of neuroimmunology》1991,34(2-3):215-222
The polymorphism at the HLA-DPB1 locus has been characterized in a large number of patients with multiple sclerosis (n = 112) and in healthy controls (n = 115). Both patients and controls lived in the southwest of France (in the Pyrénées Atlantiques) and had similar ethnic background. The typing procedure involved the selective amplification of the second exon of the DPB1 locus by polymerase chain reaction, followed by hybridization of the amplified DNA with 14 sequence-specific oligonucleotide probes. Individual alleles were identified by the pattern of hybridization of the different probes. The distribution of the DPB1 alleles was not significantly different in multiple sclerosis patients and controls (p = 0.11). This does not corroborate the reported association of multiple sclerosis with the primed lymphocyte typing (PLT)-defined DPw4 specificity and is not in favour of a role played by polymorphic residues of the DP molecule in susceptibility to multiple sclerosis. 相似文献
8.
PTH has diverse effects on bone metabolism: anabolic when given intermittently, catabolic when given continuously. The cellular
mechanisms underlying the varying target cell response are not clear yet. PTH induces RGS-2, a member of the Regulator of
G-protein Signaling protein family, via cAMP/PKA, and inactivates PKC-mediated signaling. To investigate intracellular signaling
pathways with different PTH concentration-time patterns, we treated UMR 106-01 osteoblast-like cells in a perfusion system.
PTH was administered intermittently (4 min/h, 10−7 M) or continuously at an equivalent cumulative dose (6.6 × 10−9 M). cAMP was measured using radioimmunoassay, mRNA levels using real-time rtPCR and ribonuclease protection assay, and protein
levels using Western immunoblotting. A single PTH pulse transiently increased cAMP levels by 2000% ± 1200%. In contrast to
continuous PTH exposure, cAMP induction remained unchanged with intermittent PTH, ruling out desensitization of the PTH receptor.
In continuously perfused cells, RGS-2 abundance was three to five times higher than in cells intermittently exposed to PTH
for up to 12 h. MKP-1 and -3 were significantly less induced with pulsatile PTH; exposure-mode-dependent differences in MMP-13
and IGFBP-5 were small. Pulsatile but not continuous PTH administration prevents PTHrP receptor desensitization and accumulation
of RGS-2 in osteoblasts, which should preserve PKC-dependent signaling. 相似文献
9.
肝癌多药耐药产生与低糖环境的关系 总被引:5,自引:1,他引:4
目的探讨局部微环境低糖与肝细胞癌多药耐药性(MDR)产生的关系及影响机制。方法低糖培养HepG2细胞,应用流式细胞术Annexin V/PI法检测低糖培养的细胞在化疗药物5-氟脲嘧啶(5-Fu)作用后的凋亡情况,分别应用荧光定量聚合酶链反应(PCR)技术和Western blot技术检测低糖培养后HepG2细胞内多药耐药相关基因mdr1、MRP1、LRP的mRNA和蛋白水平的表达。结果在低糖环境下生长时间越长的HepG2细胞对5-Fu的抵抗越强,而且随着低糖培养时间的增加,5-Fu诱导的HepG2细胞的凋亡高峰延迟。低糖培养的HepG2细胞内多药耐药相关基因mdr1、MRP1、LRP在mRNA和蛋白水平的表达随低糖培养时间的延长而升高,以LRP的改变最为显著。结论肝癌生长微环境葡萄糖耐量不足也是肝癌产生MDR的原因之一。低糖可通过上调一组多药耐药相关基因的表达而诱导肝癌的多药耐药性。 相似文献
10.
瘦蛋白 (leptin)是由肥胖基因编码、脂肪细胞分泌的一种分子量为 16kDa的蛋白质 ,是一种重要的代谢调节信号 ,对人和动物的采食量、能量代谢、繁殖性能等具有重要调节功能 ,对人肥胖病的治疗和改善动物的生产性能、胴体组成等有良好的潜在应用前景 .主要概述了瘦蛋白基因的克隆、转录、表达调控以及瘦蛋白受体与信号转导等分子生物学特性 相似文献