全文获取类型
收费全文 | 15060篇 |
免费 | 1579篇 |
国内免费 | 709篇 |
专业分类
耳鼻咽喉 | 164篇 |
儿科学 | 693篇 |
妇产科学 | 190篇 |
基础医学 | 4336篇 |
口腔科学 | 167篇 |
临床医学 | 1193篇 |
内科学 | 2816篇 |
皮肤病学 | 473篇 |
神经病学 | 975篇 |
特种医学 | 198篇 |
外国民族医学 | 6篇 |
外科学 | 591篇 |
综合类 | 1731篇 |
现状与发展 | 6篇 |
预防医学 | 448篇 |
眼科学 | 396篇 |
药学 | 602篇 |
1篇 | |
中国医学 | 60篇 |
肿瘤学 | 2302篇 |
出版年
2024年 | 43篇 |
2023年 | 233篇 |
2022年 | 534篇 |
2021年 | 662篇 |
2020年 | 608篇 |
2019年 | 602篇 |
2018年 | 503篇 |
2017年 | 567篇 |
2016年 | 610篇 |
2015年 | 668篇 |
2014年 | 879篇 |
2013年 | 1022篇 |
2012年 | 789篇 |
2011年 | 816篇 |
2010年 | 682篇 |
2009年 | 712篇 |
2008年 | 770篇 |
2007年 | 724篇 |
2006年 | 735篇 |
2005年 | 669篇 |
2004年 | 621篇 |
2003年 | 566篇 |
2002年 | 491篇 |
2001年 | 474篇 |
2000年 | 338篇 |
1999年 | 381篇 |
1998年 | 367篇 |
1997年 | 293篇 |
1996年 | 220篇 |
1995年 | 193篇 |
1994年 | 137篇 |
1993年 | 96篇 |
1992年 | 61篇 |
1991年 | 68篇 |
1990年 | 38篇 |
1989年 | 29篇 |
1988年 | 24篇 |
1987年 | 15篇 |
1986年 | 10篇 |
1985年 | 19篇 |
1984年 | 12篇 |
1983年 | 8篇 |
1982年 | 14篇 |
1981年 | 12篇 |
1980年 | 11篇 |
1979年 | 6篇 |
1978年 | 3篇 |
1977年 | 5篇 |
1976年 | 3篇 |
1970年 | 5篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
71.
72.
Stefan Somlo 《Clinical and experimental nephrology》1998,2(3):211-217
Conclusion The past decade has seen extraordinary progress in the study of autosomal-dominant polycystic kidney disease. The 2 major
genes for this disorder have been identified. Animal models of ADPKD have been produced. The molecular basis of the disease
has been characterized. ADPKD is a “second-hit” disease, much like many cancer predisposition syndromes. This has profound
implications for our understanding. The progression of ADPKD in individual patients is likely related more to their individual
rate of acquisition of second hits at thePKD1 orPKD2 locus than to the inherited germ line mutation itself. Therapeutic approaches will perhaps now be considered, which will
include interventions that may limit the rate at which somatic mutations occur in the kidney. The major focus of research
at present is to elucidate the normal functions ofPKD1 andPKD2. Protein binding partners are being sought for both proteins. The possible calcium channel function ofPKD2 is being investigated. The downstream effects of cellular deficiency of either protein are likely to yield many clues. Modifying
genetic factors that may independently affect disease progression are likely to be identified using the several mouse models.
Perhaps the next decade will bring great strides in understanding and in potential therapy for this common disease.
This paper was presented at the 2nd International Forum “The Frontiers of Nephrology,” Tokyo, May 10, 1998. 相似文献
73.
肾发育不良和肾发育不全(RAH)是先天性肾脏与尿路畸形(CAKUT)的主要表现之一,是导致儿童慢性肾脏病的重要原因。遗传因素与发病密切相关,随着全基因检测技术的发展,越来越多与RAH相关的基因突变被报道,GREB1L基因突变已被证实可导致RAH。本研究报道了1例后天性单侧肾萎缩GREB1L基因c.4688A>G杂合突变患儿,并复习相关文献。该患儿基因突变源自母亲,该变异为罕见变异,并且具有不完全外显特性,多种蛋白质危害预测软件预测该突变为有害变异。本文发现了新的GREB1L基因突变位点,可能拓展了与RAH相关的基因突变谱和临床谱。 相似文献
74.
甲叉四氢叶酸还原酶C677T与精神分裂症的连锁不平衡研究 总被引:2,自引:0,他引:2
目的 通过对甲叉四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)C677T错义突变与精神分裂症的连锁不平衡研究,探讨该突变与精神分裂症的关系。方法 对115个精神分裂症同胞及核心家系中,用XDT和MAPMAKER/SIBS软件系统进行MTHFRC677T与精神分裂症的连锁不平衡分析。按照不同的诊断范围将家系分类,分别在全体家系及发病年龄小于25岁的家系中进行连锁不平衡分析。结果 在4种不同的诊断分类下,对全体家系进行连锁不平衡分析未发现阳性结果。对发病年龄小于25岁的患者家系进行分析时发现,在4种不同的诊断灵感上均具有显著性意义,P值分别小于0.05及0.01。结论 MTHFR C677T错义突变可能为影响精神分裂症易感性的基因之一,尤其是在发病年龄较早的患病群体中。 相似文献
75.
Karen W. Gripp Lindsey A. Morse Marni Axelrad Kathryn C. Chatfield Aaron Chidekel William Dobyns Daniel Doyle Bronwyn Kerr Angela E. Lin David D. Schwartz Barbara J. Sibbles Dawn Siegel Suma P. Shankar David A. Stevenson Mihir M. Thacker K. Nicole Weaver Sue M. White Katherine A. Rauen 《American journal of medical genetics. Part A》2019,179(9):1725-1744
Costello syndrome (CS) is a RASopathy caused by activating germline mutations in HRAS. Due to ubiquitous HRAS gene expression, CS affects multiple organ systems and individuals are predisposed to cancer. Individuals with CS may have distinctive craniofacial features, cardiac anomalies, growth and developmental delays, as well as dermatological, orthopedic, ocular, and neurological issues; however, considerable overlap with other RASopathies exists. Medical evaluation requires an understanding of the multifaceted phenotype. Subspecialists may have limited experience in caring for these individuals because of the rarity of CS. Furthermore, the phenotypic presentation may vary with the underlying genotype. These guidelines were developed by an interdisciplinary team of experts in order to encourage timely health care practices and provide medical management guidelines for the primary and specialty care provider, as well as for the families and affected individuals across their lifespan. These guidelines are based on expert opinion and do not represent evidence‐based guidelines due to the lack of data for this rare condition. 相似文献
76.
Overexpression of S100A4 is closely related to the aggressiveness of gastric cancer 总被引:25,自引:0,他引:25
Cho YG Nam SW Kim TY Kim YS Kim CJ Park JY Lee JH Kim HS Lee JW Park CH Song YH Lee SH Yoo NJ Lee JY Park WS 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2003,111(5):539-545
Elevated levels of the calcium-binding protein S100A4 cause metastasis of benign rat mammary tumor cells. To investigate whether S100A4 plays an important role in the invasion and metastasis of gastric cancers, we examined the gene mutations in the coding regions and expression patterns of the S100A4 in gastric adenocarcinoma in Korea. Moderate to strong expression of S100A4 was found in 53 (68.8%) of the 77 gastric adenocarcinomas, whilst normal gastric epithelium either failed to stain or showed weak staining. Interestingly, S100A4 expression was more frequently observed in gastric cancer patients with advanced gastric cancer (p=0.039), positive lymph node metastasis (p=0.001), and peritoneal dissemination (p=0.022). No gene mutations were found in the analyzed genomic area in 77 gastric adenocarcinomas and 15 gastric cancer cell lines. We found one single nucleotide polymorphism without an amino acid change, A99G, in two cases. These data suggest that the overexpression of S100A4 may be closely related to the aggressiveness of gastric cancer in Korea. 相似文献
77.
We investigated 10 unrelated Chinese patients with type 2 Gaucher disease and performed ex vivo expression for the novel mutations to characterize their functional defects. These patients were diagnosed by enzymatic assays and clinicopathologic features over the past five years in a national centre in China. Genomic DNA was sequenced by a two-stage PCR approach for mutations in the functional GBA gene. Novel mutations were expressed with baculovirus-transfected Sf21 cells. Six novel mutations were found (in traditional nomenclature): P122L, Y363C, N382K, L383R, L385P, and M416V. Review of reported mutations indicated clustering of type 2 mutations in three regions of the GBA gene. Expression of novel mutations revealed that the enzyme defect could arise from one of two mechanisms: loss of catalytic activity (Y363C and M416V) or enzyme instability (P122L and N382K). 相似文献
78.
Classic Ehlers-Danlos syndrome (EDS) is characterized by fragile and hyperextensible skin, atrophic scarring, and joint hypermobility. Mutations in the COL5A1 and the COL5A2 gene encoding the alpha1(V) and the alpha2(V) chains, respectively, of type V collagen have been shown to cause the disorder, but it is unknown what proportion of classic EDS patients carries a mutation in these genes. We studied fibroblast cultures from 48 patients with classic EDS by SDS-PAGE for the presence of type V collagen defects. An abnormal collagen pattern was detected in only 2 out of 48 cell lines, making this a poor method for routine diagnostic evaluation. A total of 42 out of 48 (88%) patients were heterozygous for an expressed polymorphic variant in COL5A1. cDNA from 18 (43%) of them expressed only one COL5A1 allele. In 37 patients, the COL5A1/A2 genes were then analyzed by SSCP and conformation sensitive gel electrophoresis (CSGE). A total of 26 patients that were mutation-negative after SSCP/CSGE screening were reanalyzed by dHPLC. In addition, 11 other patients were analyzed by dHPLC only. In total, 17 mutations leading to a premature stop codon and five structural mutations were identified in the COL5A1 and the COL5A2 genes. In three patients with a positive COL5A1 null-allele test, no causal mutation was found. Overall, in 25 out of 48 patients (52%) with classic EDS, an abnormality in type V collagen was confirmed. Variability in severity of the phenotype was observed, but no significant genotype-phenotype correlations emerged. The relatively low mutation detection rate suggests that other genes are involved in classic EDS. We excluded the COL1A1, COL1A2, and DCN gene as major candidate genes for classic EDS, since no causal mutation in these genes was found in a number of patients who tested negative for COL5A1 and COL5A2. 相似文献
79.
Gao HZ Kobayashi K Tabata A Tsuge H Iijima M Yasuda T Kalkanoglu HS Dursun A Tokatli A Coskun T Trefz FK Skladal D Mandel H Seidel J Kodama S Shirane S Ichida T Makino S Yoshino M Kang JH Mizuguchi M Barshop BA Fuchinoue S Seneca S Zeesman S Knerr I Rodés M Wasant P Yoshida I De Meirleir L Abdul Jalil M Begum L Horiuchi M Katunuma N Nakagawa S Saheki T 《Human mutation》2003,22(1):24-34
Classical citrullinemia (CTLN1), a rare autosomal recessive disorder, is caused by mutations of the argininosuccinate synthetase (ASS) gene, localized on chromosome 9q34.1. ASS functions as a rate-limiting enzyme in the urea cycle. Previously, we identified 32 mutations in the ASS gene of CTLN1 patients mainly in Japan and the United States, and to date 34 different mutations have been described in 50 families worldwide. In the present study, we report ASS mutations detected in 35 additional CTLN1 families from 11 countries. By analyzing the entire coding sequence and the intron-exon boundaries of the ASS gene using RT-PCR and/or genomic DNA-PCR, we have identified 16 novel mutations (two different 1-bp deletions, a 67-bp insertion, and 13 missense) and have detected 12 known mutations. Altogether, 50 different mutations (seven deletion, three splice site, one duplication, two nonsense, and 37 missense) in 85 CTLN1 families were identified. On the basis of primary sequence comparisons with the crystal structure of E. coli ASS protein, it may be concluded that any of the 37 missense mutations found at 30 different positions led to structural and functional impairments of the human ASS protein. It has been found that three mutations are particularly frequent: IVS6-2A>G in 23 families (Japan: 20 and Korea: three), G390R in 18 families (Turkey: six, U.S.: five, Spain: three, Israel: one, Austria: one, Canada: one, and Bolivia: one), and R304W in 10 families (Japan: nine and Turkey: one). Most mutations of the ASS gene are "private" and are distributed throughout the gene, except for exons 5 and 12-14. It seems that the clinical course of the patients with truncated mutations or the G390R mutation is early-onset/severe. The phenotype of the patients with certain missense mutations (G362V or W179R) is more late-onset/mild. Eight patients with R86H, A118T, R265H, or K310R mutations were adult/late-onset and four of them showed severe symptoms during pregnancy or postpartum. However, it is still difficult to prove the genotype-phenotype correlation, because many patients were compound heterozygotes (with two different mutations), lived in different environments at the time of diagnosis, and/or had several treatment regimes or various knowledge of the disease. 相似文献
80.
An intact enteric nervous system is required for normal gastrointestinal tract function. Several human conditions result from decreased innervation by enteric neurons; however, the genetic basis of enteric nervous system development and function is incompletely understood. In an effort to increase our understanding of the mechanisms underlying enteric nervous system development, we screened mutagenized zebrafish for changes in the number or distribution of enteric neurons. We also established a motility assay and rescreened mutants to learn whether enteric neuron number is correlated with gastrointestinal motility in zebrafish. We describe mutations isolated in our screen that affect enteric neurons specifically, as well as mutations that affect other neural crest derivatives or have pleiotropic effects. We show a correlation between the severity of enteric neuron loss and gastrointestinal motility defects. This screen provides biological tools that serve as the basis for future mechanistic studies. 相似文献