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青岛大学附属烟台毓璜顶医院生殖医学中心对1例反复体外受精/卵细胞质内单精子注射(IVF/ICSI)助孕后早期胚胎发育停滞的患者进行了全外显子基因检测,发现了一种新的TUBB8基因突变型(c.208C>T/p.Pro70Ser),并进一步探讨了TUBB8基因突变与早期胚胎发育停滞之间的联系,为反复种植失败的诊断与治疗提供更多可能性。 相似文献
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L. Samuel Hellgren Martin Hysek Kenbugul Jatta Jan Zedenius C. Christofer Juhlin 《Head and neck pathology》2021,15(2):668
Benign thyroid lesions such as multinodular goiter and adenomatoid nodules are well-circumscribed lesions displaying a macrofollicular growth pattern and lack of nuclear atypia. The highly unusual macrofollicular variant of follicular thyroid carcinoma (MV-FTC) mirrors these attributes and is thereby misclassified by cytological examination of fine-needle aspiration biopsies. The MV-FTC diagnosis is instead suggested following histological investigation, in which malignant attributes, most commonly capsular invasion, are noted. The bulk of MV-FTCs described in the literature arise in younger female patients and carry an excellent prognosis. A recent coupling to mutations in the DICER1 tumor suppressor gene has been proposed, possibly indicating aberrancies in micro-RNA (miRNA) patterns as responsible of the tumorigenic process. We describe the cytological, histological and molecular phenotype of a 35 mm large MV-FTC arising in the right thyroid lobe of a 33-year-old female with a family history of multinodular goiter. The tumor was encapsulated and strikingly inconspicuous in terms of cellularity and atypia, but nevertheless displayed multiple foci with capsular invasion. A next-generation molecular screening of tumor DNA revealed missense variants in DICER1 (p. D1709N) and MET (p. T1010I), but no established fusion gene events. After sequencing of germline DNA, the DICER1 mutation was confirmed as somatic, while the MET variant was constitutional. The patient is alive and well, currently awaiting radioiodine treatment. This MV-FTC mirrors previous publications, suggesting that these tumors carry a favorable prognosis and predominantly arise in younger females. Moreover, DICER1 mutations should be considered a common driver event in the development of MV-FTCs. 相似文献
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Takahashi S Okada K Nagasawa H Shimada Y Sakamoto H Itoi E 《Virchows Archiv : an international journal of pathology》2004,444(5):454-458
We describe a case history of a 24-year-old male with osteogenesis imperfecta (OI) who developed osteosarcoma of the left thigh. High-dose ifosfamide therapy caused marked tumor regression of multiple lung metastases. Immunohistochemically, the tumor cells were diffusely positive for the p53 protein. Mutation of the p53 gene was not detected by direct genomic sequencing of exons 4–8. The radiographic characteristics, including irregularly distributed osteolytic lesions and cortical discontinuity, should not be confused with hyperplastic callus formation, a benign process. A biopsy is critical to establish the differential diagnosis between osteosarcoma and common hyperplastic callus formation in OI; however, it must be applied with great care. 相似文献
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Evaluating the mutagenic potential of chemicals the minimal battery and extrapolation problems 总被引:1,自引:0,他引:1
F. H. Sobels 《Archives of toxicology》1980,46(1-2):21-30
During the past ten years growing concern about damage to DNA as an important cause of human ill-health has resulted in an explosive development of the field of genetic toxicology. Adequate regulations to restrict exposure to chemical mutagens require recognition and evaluation of mutagenic activity. For this purpose a qualitative and an extrapolation phase can be distinguished. For the qualitative phase, the minimal battery should consist of at least three tests, that is: (1) tests for gene- or point mutations in bacteria (Salmonella or E. coli) with and without metabolic activation; (2) two tests for point mutations in eukaryotes, or (3) one such test and a test for the detection of chromosome aberrations in mammalian cells in vitro. Depending on experience and facilities, a choice of two can be made out of the following four test systems: (1) Tests for point mutations in mammalian cells in vitro, with and without metabolic activation (deficiency for HGPRT, or TK); (2) the sex-linked recessive lethal test with Drosophila melanogaster; (3) tests with yeast, Saccharomyces cerevisiae, for point mutations, with and without metabolic activation; (4) tests for chromosome aberrations in mammalian cells in vitro, with and without metabolic activation. Two different metabolic activation systems should be employed. For further selection of more sensitive test systems, studies on comparative mutagenesis are considered important. A mammalian test for chromosome aberrations in vivo is not included in this minimal battery. Since under in vivo conditions considerably lower concentrations have to be employed than in vitro, it seems unlikely that positive results will be obtained with an in vivo mammalian cytogenetic assay, following negative results in an in vitro cytogenetic assay or in two different tests for point mutations. The finding that the effective concentration for the production of chromosome breakage events differs from that required to induce point mutations (the two-level effect) will be briefly discussed. When mutagenic compounds are indispensible or, in the case of ubiquitous exposure, a quantification of risks becomes necessary and here one is confronted with many difficulties. Information on damage that is hard to measure directly can be obtained in an indirect way by comparison with end-points that can be determined experimentally, such as alkylation per nucleotide.
Names of chemical substances tested: hydroxylamine; diepoxybutane; N-ethyl-N-nitrosourea; methylmethanesulfonate (MMS); DEN; Mitomycin C; Procarbazine; atrazine; benz(a)pyrene; EMS; pyrolitic products; flavonoids; mycotoxins; nitrosamines; TEMGiven at the International Conference Mutagenicity Testing of Pharmaceuticals: Present Status, Paris, 12–14 March, 1980, sponsored by the Fondation de l'Industrie Pharmaceutique pour la Recherche 相似文献
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A. L. Catapano A. Corsini M. Mazzotti A. Granata P. Uboldi F. M. Maggi L. Romano C. Romano S. Fantappiè R. Fumagalli 《European journal of epidemiology》1992,8(Z1):26-32
Familial defective apolipoprotein B-100 (FDB) is a genetic disorder presenting with hypercholesterolemia and abnormal low density lipoprotein (LDL) that binds poorly to LDL receptors. This disease appears to be caused by a mutation in the apo B gene. In the present study thirteen members of a family with moderate hypercholesterolemia (250–350 mg/dl) were investigated. Biochemical studies on cultured skin fibroblasts ruled out classical familial hypercholesterolemia (receptor deficiency). LDL from nine affected members displayed, in an in vitro cell binding assay, a reduced affinity (2.5 fold) for the receptor, and had normal electrophoretic mobility, size and chemical composition. Lp(a) levels in family members were comparable to those present in normolipidemics and lower than those observed in primary hypercholesterolemia. The disorder is transmitted over three generations as an autosomal codominant trait and all the affected members are heterozygotes and hypercholesterolemic.Corresponding author. 相似文献
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目的 寻找山东籍Wilson病患者WND基因突变热点,以便易于用SSCP及酶切分析方法检出。使无先证者及独生子女家系易于作出基因诊断,同时可用于杂合子筛查。方法 PCR扩增WND基因8号外显子778密码子区域,SSCP检洲点突变,用MSPI内切酶进一步验证G-T突变的正确性。结果 13例Wilson患者,检出778密码子G-T纯合突变2例,杂舍突变7例,未突变4例,共计26条染色体,突变染色体11条,总染色体突变率为42.3%。结论 WND基因8号外显子,778密码子G-T突变是山东WD患者的一个突变热点。SSCP和酶切分析是诊断此位点突变的便捷方法,可用于WD患者及杂合子检出。 相似文献