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31.
Human multiple myeloma cells express peroxisome proliferator-activated receptor gamma and undergo apoptosis upon exposure to PPARgamma ligands 总被引:8,自引:0,他引:8
Multiple myeloma is essentially an incurable malignancy and it is therefore of great interest to develop new therapeutic approaches. We previously reported that human B cell-lymphomas express the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) and are killed by PPARgamma ligands. Herein, we investigate the therapeutic potential of PPARgamma ligands for multiple myeloma. The human multiple myeloma cell lines ANBL6 and 8226 express PPARgamma mRNA and protein. The PPARgamma ligands, 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) and ciglitazone, induced multiple myeloma cell apoptosis as determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, loss of mitochondrial membrane potential, and caspase activation. Importantly, the ability of PPARgamma ligands to kill both multiple myeloma cell lines was not abrogated by Interleukin-6 (IL-6), a multiple myeloma growth survival factor. Finally, the RXR ligand 9-cis retinoic acid (9-cis RA) in combination with PPARgamma ligands greatly enhanced multiple myeloma cell killing. These new findings support that PPARgamma ligands may represent a novel therapy for multiple myeloma. 相似文献
32.
宁夏回族人群X染色体10个短串联重复序列位点的遗传多态性调查 总被引:7,自引:2,他引:7
目的研究宁夏回族群体X染色体上的10个短串联重复序列(DXS101、DXS6789、DXS6799、DXS6804、DXS7130、DXS7132、DXS7133、DXS7423、HPRTB、DXS8378)的基因及基因型频率分布。方法随机抽取100名宁夏回族无关个体静脉血,提取DNA,PCR扩增,变性聚丙烯酰胺凝胶电泳,银染检测结果。结果DXS101、DXS6789、DXS6799、DXS6804、DXS7130、DXS7132、DXS7133、DXS7423、HPRTB、DXS8378分别检出9、8、4、6、6、6、4、4、5和5种等位基因;分别检出17、22、7、14、14、15、6、7、12和8种基因型;基因频率分别分布在0.0087~0.3130、0.0087~0.2696、0.0348~0.5826、0.0087~0.3044、0.0261~0.4348、0.0261~0.3217、0.0261~0.6783、0.0087~0.4870、0.0261~0.4783、0.0087~0.4870之间;此10个位点女性的基因型频率分布均符合Hardy-Weinberg平衡,多态信息量除DXS7133和DXS7423外均大于0.50;女性个体识别率从0.89(DXS7133,DXS7423)至0.99(DXS101,DXS6789,DXS7132)。结论这10个X染色体短串联重复序列位点有较高的个体识别率,在个体识别和女孩亲权鉴定中有较高应用价值,对疾病相关研究有重要意义。 相似文献
33.
Valledor AF 《Immunobiology》2005,210(2-4):127-132
Macrophages play essential roles in infection and resolution of inflammation. This review summarizes recent findings that suggest a relevant role for the nuclear receptor liver X receptor (LXR) in the evolution of immune responses. By exerting both positive and negative regulation of specific macrophage gene expression networks, LXRs display anti-inflammatory activities and promote macrophage survival in bacterial infection settings. Agonists that activate the LXR pathway may be used to enhance innate immunity to highly virulent pathogens that otherwise induce macrophage apoptosis as a means to subvert host immune defense. 相似文献
34.
目的:通过分析16例结核性脑膜炎的CT表现及其产生的病理基础,提高对本病的认识和诊断水平。方法:16例结核性脑膜炎病人采用常规头颅CT扫描,对其影像及临床资料进行回顾性分析。结果:脑基底池、侧裂池变窄12例(75%),合并密度增高8例(50%);不同程度的脑积水14例(88%);脑梗塞8例(50%);结核瘤1例(6%)。结论:结核性脑膜炎的主要CT征象是脑基底池、侧裂池变窄,同时有不同程度的脑积水。如同时伴有脑结核瘤,可作出诊断。 相似文献
35.
Florence P. Haseltine Vincent A. Lynch Daniel L. Van Dyke W. Roy Breg Uta Francke John M. Opitz 《American journal of medical genetics. Part A》1982,13(2):115-123
Cells from three patients with early gonadal failure and a balanced reciprocal translocation involving the long arm of the X chromosome and an autosome were studied. Fibroblasts from a patient with a similar balanced reciprocal translocation but normal reproductive capabilities were also studied. Two of the four patients were found to have serologically detectable H-Y antigen on their cells. Since H-Y antigen has been found on the cells of other patients with X chromosome abnormalities but without a Y chromosome, it is thought that the X chromosome plays a role in the regulation of H-Y antigen expression. This study suggests that the long arm of the X chromosome may be involved but the location of a regulatory gene cannot be identified in these studies. These cases do not permit us to implicate H-Y antigen as a cause of gonadal dysgenesis and early gonadal failure in females who have structurally abnormal X chromosomes. 相似文献
36.
Krueger S Kalinski T Hundertmark T Wex T Küster D Peitz U Ebert M Nägler DK Kellner U Malfertheiner P Naumann M Röcken C Roessner A 《The Journal of pathology》2005,207(1):32-42
Recently, we identified increased cathepsin X expression in H. pylori-infected gastric mucosa. Here, we describe further up-regulation in gastric cancer and report on the role of inflammatory cytokines required for cathepsin X up-regulation in H. pylori-infected gastric mucosa, as well as on consequences for cellular invasion. Biopsy specimens were taken from the antrum, corpus and cardia of H. pylori-infected and non-infected patients. Gastric cancer samples were obtained from patients undergoing gastric surgery. Cathepsin X was detected in gastric mucosa by quantitative real-time RT-PCR, western blotting and immunohistochemistry. Induction of cathepsin X expression in epithelial and inflammatory cells caused by H. pylori infection was tested in in vitro contact and non-contact co-cultures of AGS cells and monocytic cells. Patients with H. pylori gastritis showed significantly higher cathepsin X mRNA (2.5-fold) and protein (1.6-fold) expression than H. pylori-negative patients. Cathepsin X was also up-regulated in gastric cancer (3-12-fold) compared to non-neoplastic mucosa. Cathepsin X was predominantly expressed by macrophages in the mucosal stroma and in glands of the antral mucosa. In addition, tumour cells stained for cathepsin X in 26 (68%) patients with gastric carcinoma. In general, staining was significantly more common (20 vs. 6 patients) and more intense (3.55 vs. 0.83) in intestinal type gastric cancer than in the diffuse type. In vitro cell culture experiments revealed that intercellular signalling between pathogenicity island (PAI)-positive H. pylori-infected epithelial cells and macrophages via soluble factors in the culture medium seems to be responsible for increased expression of cathepsin X in monocytes. Using antisense oligonucleotides, cathepsin X up-regulation was directly associated with higher invasiveness in vitro. Although no correlation of cathepsin X expression and TNM stage was found, our study demonstrates that cathepsin X plays a role not only in the chronic inflammation of gastric mucosa but also in the tumourigenesis of gastric cancer. 相似文献
37.
Klinefelter syndrome is a common cause for mental retardation of unknown etiology among prepubertal males 总被引:1,自引:0,他引:1
Klinefelter syndrome (KS) has not typically been associated with mental retardation (MR), however, in recent years a growing body of evidence suggested that KS boys often experience language deficits and academic difficulties. In this study, we screened DNA samples from 1205 patients originally referred for fragile X syndrome (FRAX) testing, because of MR of unknown etiology and detected 8 KS patients. A similar number of males in the same age group were found to have FRAX; 3 of them had a family history of FRAX. Based on these findings, KS might be the most common cause of MR of unknown etiology among prepubertal males. Because of the significant benefits of early recognition and treatment of KS, we emphasize the importance of cytogenetic testing of all prepubertal males with cognitive impairment even without dysmorphic features. 相似文献
38.
Grant R. Sutherland Elizabeth Baker Antonio Fratini John M. Opitz James F. Reynolds 《American journal of medical genetics. Part A》1985,22(2):433-443
Folate sensitive fragile sites on human chromosomes have been found to be inducible in cultured lymphocytes by high levels of thymidine but not by high levels of BrdU. The biochemical interpretation of events leading to fragile site expression has been revised since it is now clear that low levels of either thymidylate or deoxycytidine triphosphate will result in this phenomenon. A model for the DNA at a fragile site, composed of alternating repeating polypurine/polypyrimidine sequences is proposed. 相似文献
39.
40.
Natsuo Yasui Keiichi Ozono Masayo Yamagata Hidehiko Kawabata Hideki Yoshikawa 《American journal of medical genetics. Part A》2001,99(4):328-330
A 23‐year‐old man was diagnosed as having X‐linked spondyloepiphyseal dysplasia tarda (SEDT; MIM 313400) based on his disproportionately short trunk, short stature, characteristic radiological features of the spine (posterior hump, end plate sclerosis, and disc space narrowing) and the hips (short and thick femoral necks), and positive family history. This Japanese family was found to have an intragenic deletion flanking intron 2 and exon 3 of the SEDL gene that not only included the 5′ untranslated region but also the coding sequence for the first methionine through the 25th alanine. This mutation was present in the proband and his unaffected mother (a heterozygote), but not in an unaffected sister and an unaffected uncle. The nature of the mutation predicted that the SEDL protein (Sedlin) was not produced in the proband, indicating that loss of Sedlin caused SEDT. © 2001 Wiley‐Liss, Inc. 相似文献