全文获取类型
收费全文 | 23104篇 |
免费 | 1725篇 |
国内免费 | 90篇 |
专业分类
耳鼻咽喉 | 158篇 |
儿科学 | 790篇 |
妇产科学 | 533篇 |
基础医学 | 3355篇 |
口腔科学 | 342篇 |
临床医学 | 2812篇 |
内科学 | 5102篇 |
皮肤病学 | 483篇 |
神经病学 | 2440篇 |
特种医学 | 411篇 |
外科学 | 2073篇 |
综合类 | 130篇 |
一般理论 | 28篇 |
预防医学 | 2534篇 |
眼科学 | 249篇 |
药学 | 1567篇 |
中国医学 | 43篇 |
肿瘤学 | 1869篇 |
出版年
2024年 | 16篇 |
2023年 | 199篇 |
2022年 | 352篇 |
2021年 | 770篇 |
2020年 | 513篇 |
2019年 | 768篇 |
2018年 | 794篇 |
2017年 | 584篇 |
2016年 | 662篇 |
2015年 | 725篇 |
2014年 | 922篇 |
2013年 | 1208篇 |
2012年 | 1963篇 |
2011年 | 1969篇 |
2010年 | 1049篇 |
2009年 | 883篇 |
2008年 | 1543篇 |
2007年 | 1593篇 |
2006年 | 1563篇 |
2005年 | 1443篇 |
2004年 | 1338篇 |
2003年 | 1186篇 |
2002年 | 1044篇 |
2001年 | 151篇 |
2000年 | 98篇 |
1999年 | 162篇 |
1998年 | 191篇 |
1997年 | 138篇 |
1996年 | 135篇 |
1995年 | 123篇 |
1994年 | 85篇 |
1993年 | 88篇 |
1992年 | 48篇 |
1991年 | 50篇 |
1990年 | 44篇 |
1989年 | 55篇 |
1988年 | 39篇 |
1987年 | 28篇 |
1986年 | 40篇 |
1985年 | 30篇 |
1984年 | 48篇 |
1983年 | 28篇 |
1982年 | 26篇 |
1981年 | 26篇 |
1980年 | 23篇 |
1979年 | 17篇 |
1978年 | 16篇 |
1976年 | 18篇 |
1973年 | 18篇 |
1972年 | 16篇 |
排序方式: 共有10000条查询结果,搜索用时 203 毫秒
151.
Bardaro T Falco G Sparago A Mercadante V Gean Molins E Tarantino E Ursini MV D'Urso M 《Human mutation》2003,21(1):8-11
Familial incontinentia pigmenti (IP) is a rare X-linked dominant disorder that affects ectodermal tissues. Over 90% of IP carrier females have a recurrent genomic deletion of exons 4-10 of the NEMO (IKBKG-IKKgamma) gene, which encodes a regulatory component of the IkB kinase complex, required to activate the NF-kB pathway. In IP, mutations in NEMOlead to the complete loss of NF-kB activation creating a susceptibility to cellular apoptosis in response to TNF-alpha. This condition is lethal for males during embryogenesis while females, who are mosaic as a result of X-inactivation, can survive. Recently, a second nonfunctional copy of the gene, DeltaNEMO, was identified, opposite in direction to NEMO in a 35.5-kb duplicated sequence tract. PCR-based detection of the NEMO deletion is diagnostic for IP disease. However, we present instances in which ex 4-10 DeltaNEMO pseudogene deletion occurs in unaffected parents of two females with clinically characteristic IP. These were missed by the currently standard PCR-based method, but can be easily discriminated by a new PCR-based test reported here that permits unambiguous molecular diagnosis and proper familial genetic counseling for IP. 相似文献
152.
Human defensins 总被引:7,自引:0,他引:7
Schneider JJ Unholzer A Schaller M Schäfer-Korting M Korting HC 《Journal of molecular medicine (Berlin, Germany)》2005,83(8):587-595
Antimicrobial peptides are small, cationic, amphiphilic peptides of 12–50 amino acids with microbicidal activity against both bacteria and fungi. The eukaryotic antimicrobial peptides may be divided into four distinct groups according to their structural features: cysteine-free -helices, extended cysteine-free -helices with a predominance of one or two amino acids, loop structures with one intramolecular disulfide bond, and -sheet structures which are stabilised by two or three intramolecular disulfide bonds. Mammalian defensins are part of the last-mentioned group. The mammalian defensins can be subdivided into three main classes according to their structural differences: the -defensins, -defensins and the recently described -defensins. Mammalian -defensins are predominantly found in neutrophils and in small intestinal Paneth cells, whereas mammalian -defensins have been isolated from both leukocytes and epithelial cells. Recently, two novel human -defensins, human beta-defensin-3 (HBD-3), and human beta-defensin-4 (HBD-4) have been discovered. Similar to HBD-1 and HBD-2, HBD-3 has microbicidal activity towards the Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli) and the yeasts Candida albicans and Malassezia furfur. In addition, HBD-3 kills Gram-positive bacteria such as Streptococcus pyogenes or Staphylococcus aureus, including multi-resistant S. aureus strains, and even vancomycin-resistant Enterococcus faecium. In contrast to HBD-1 and HBD-2, significant expression of HBD-3 has been demonstrated in non-epithelial tissues, such as leukocytes, heart and skeletal muscle. HBD-4 is expressed in certain epithelia and in neutrophils. Its bactericidal activity against P. aeruginosa is stronger than that of the other known -defensins. Here we present an overview of human antimicrobial peptides with some emphasis on their antifungal properties.J.J. Schneider and A. Unholzer contributed equally to this work 相似文献
153.
Ghiorzo P Villaggio B Sementa AR Hansson J Platz A Nicoló G Spina B Canepa M Palmer JM Hayward NK Bianchi-Scarrà G 《Human pathology》2004,35(1):25-33
Little is known about the correlation between the loss of p16 expression and tumor progression in familial melanoma; no systematic study has been conducted on p16 expression in melanocytic tumors from patients carrying germline CDKN2A mutations. We analyzed 98 early primary lesions from familial patients, previously tested for germline CDKN2A status, by quantitative immunohistochemistry using 3 p16 antibodies. We found that p16 expression was inversely correlated with tumor progression and was significantly lower in melanomas, including in situ lesions, than in nevi. Of other features analyzed, tumor thickness showed the most significant correlation with p16 levels. Lesions from mutation-negative patients displayed combined nuclear and cytoplasmic staining. However, some mutation-positive lesions (ie, G101W, 113insR, M53I, R24P, and 33ins24), including benign nevi, showed nuclear mislocalization, confirming previous studies suggesting that subcellular distribution indicates functional impairment of p16. 相似文献
154.
Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: a case study with comparison to MRI 总被引:1,自引:0,他引:1
Choe R Corlu A Lee K Durduran T Konecky SD Grosicka-Koptyra M Arridge SR Czerniecki BJ Fraker DL DeMichele A Chance B Rosen MA Yodh AG 《Medical physics》2005,32(4):1128-1139
We employ diffuse optical tomography (DOT) to track treatment progress in a female subject presenting with locally advanced invasive carcinoma of the breast during neoadjuvant chemotherapy. Three-dimensional images of total hemoglobin concentration and scattering identified the tumor. Our measurements reveal tumor shrinkage during the course of chemotherapy, in reasonable agreement with magnetic resonance images of the same subject. A decrease in total hemoglobin concentration contrast between tumor and normal tissue was also observed over time. The results demonstrate the potential of DOT for measuring physiological parameters of breast lesions during chemotherapy. 相似文献
155.
Filho OG Gordan AN Mello Rde A Neto CS Heinke T 《International journal of surgical pathology》2004,12(2):151-153
Hamartomas were first described by Albrecht in 1904, who defined them as tumor-like malformations in which there was abnormal blending of the normal components of an organ. The myoid hamartoma is a rare benign lesion of the breast and has an uncertain origin, possibly in the walls of the blood vessels, muscularis mammillae of the areolae, and mainly in myoepithelium. We report 3 cases of myoid hamartomas of the breast, with the clinical, radiologic, and histopathological findings, and review the literature. The 3 lesions showed normal breast ducts and lobules, entrapped by a muscular stroma and some foci of mature adipose tissue. The muscular origin of part of the stroma was confirmed by strong reactiveness with smooth-muscle actin. 相似文献
156.
Wong N Hui AB Fan B Lo KW Pang E Leung SF Huang DP Johnson PJ 《Cancer Genetics and Cytogenetics》2003,140(2):124-132
Nasopharyngeal carcinoma (NPC) cell lines and xenografts represent valuable models for functional and therapeutic studies on this common malignancy in Southeast Asia. The karyotypic information in most NPC cell lines and xenografts, however, remains largely unclear to date. We have characterized the chromosomal aberrations in six commonly used human NPC cell lines and xenografts using the molecular cytogenetic technique of comparative genomic hybridization (CGH). Genomic imbalances identified in cell lines were further correlated with structural abnormalities indicated from spectral karyotyping (SKY) analysis. CGH revealed consistent overrepresentations of 8q (six out of six cases) with a smallest overlapping region identified on 8q21.1q22. Other common gains included 7p (4/6 cases), 7q (4/6 cases), 12q (4/6), and 20q (4/6 cases), where minimal overlapping regions were suggested on 7p15p14, 7q11.2q21, and 12q22q24.1. Common losses were detected on 3p12p21 (4/6 cases) and 11q14qter (4/6 cases). Although SKY analysis on cell lines revealed predominantly unbalanced rearrangements, reciprocal translocations that involved chromosome 2 [i.e., t(1;2), t(2;3), and t(2;4)] were suggested. Furthermore, SKY examination illustrated additional breakpoints on a number of apparently balanced chromosomes. These breakpoints included 3p21, 3q26, 5q31, 6p21.1p25, 7p14p22, and 8q22. Our finding of regional gains and losses and breakpoints represents information that may contribute to NPC studies in vitro. 相似文献
157.
Lovering Ruth; Middleton-Price Helen R.; O'Reilly Marie-Anne J.; Genet Sally A.; Parkar Mohammed; Sweatman Angela K.; Bradley Linda D.; Alterman Lesley A.; Malcolm Sue; Morgan Gareth; Levinsky Roland J.; Kinnon Christine 《Human molecular genetics》1993,2(2):139-141
Genetic linkage analysis has been instrumental in mapping thegene for X-linked agammaglobulinemia (XLA) to the proximal longarm of the human X chromosome, to Xq22. Due to the relativerarity of this disease the localization of the gene within Xq22has remained imprecise. We have investigated twenty-nine familiesaffected by XLA and have found no recombinants with the DXS178locus in over 30 informative meioses. DXS178 is now the mostreliable and informative locus for use in pre-natal diagnosisand carrier detection of XLA. In addition, we have identifiednew closely linked proximal and distal flanking markers forXLA, DXS442 and DXS101, respectively. These loci are separatedby 2cM, considerably reducing the extent of DNA within whichthe XLA locus can be contained. This will open up the way formore directed positional cloning efforts for the isolation ofthe XLA gene. 相似文献
158.
Candida albicans expresses a focal adhesion kinase-like protein that undergoes increased tyrosine phosphorylation upon yeast cell adhesion to vitronectin and the EA.hy 926 human endothelial cell line 下载免费PDF全文
Santoni G Lucciarini R Amantini C Jacobelli J Spreghini E Ballarini P Piccoli M Gismondi A 《Infection and immunity》2002,70(7):3804-3815
The signaling pathways triggered by adherence of Candida albicans to the host cells or extracellular matrix are poorly understood. We provide here evidence in C. albicans yeasts of a p105 focal adhesion kinase (Fak)-like protein (that we termed CaFak), antigenically related to the vertebrate p125Fak, and its involvement in integrin-like-mediated fungus adhesion to vitronectin (VN) and EA.hy 926 human endothelial cell line. Biochemical analysis with different anti-chicken Fak antibodies identified CaFak as a 105-kDa protein and immunofluorescence and cytofluorimetric analysis on permeabilized cells specifically stain C. albicans yeasts; moreover, confocal microscopy evidences CaFak as a cytosolic protein that colocalizes on the membrane with the integrin-like VN receptors upon yeast adhesion to VN. The protein tyrosine kinase (PTK) inhibitors genistein and herbimycin A strongly inhibited C. albicans yeast adhesion to VN and EA.hy 926 endothelial cells. Moreover, engagement of alpha v beta 3 and alpha v beta 5 integrin-like on C. albicans either by specific monoclonal antibodies or upon adhesion to VN or EA.hy 926 endothelial cells stimulates CaFak tyrosine phosphorylation that is blocked by PTK inhibitor. A role for CaFak in C. albicans yeast adhesion was also supported by the failure of VN to stimulate its tyrosine phosphorylation in a C. albicans mutant showing normal levels of CaFak and VNR-like integrins but displaying reduced adhesiveness to VN and EA.hy 926 endothelial cells. Our results suggest that C. albicans Fak-like protein is involved in the control of yeast cell adhesion to VN and endothelial cells. 相似文献
159.
Mariano Rocchi Angela Covone Giovanni Romeo Raffaella Faraonio Vittorio Colantuoni 《Somatic Cell and Molecular Genetics》1989,15(2):185-190
The human gene coding for RBP4 has been assigned to 10q2324 using a panel of somatic cell hybrids and in situ hybridization experiments. The mapping of the human RBP1, previously assigned by our group to chromosome 3 using a panel of somatic cell hybrids, was restricted to the region 3q2122 using in situ experiments and Southern blots of genomic DNA from a hybrid retaining a portion of chromosome 3.R.F. is recipient of a Research Grant from A.I.R.C. 相似文献
160.
Matrix metalloproteinase-2, -9, and tissue inhibitor of metalloproteinase-1 in patients with hypertension. 总被引:6,自引:0,他引:6
Giuseppe Derosa Angela D'Angelo Leonardina Ciccarelli Mario N Piccinni Fabio Pricolo Sibilla Salvadeo Lorenza Montagna Alessia Gravina Ilaria Ferrari Simona Galli Sonia Paniga Carmine Tinelli Arrigo F G Cicero 《Endothelium》2006,13(3):227-231
There are conflicting data in the literature regarding the expression pattern of the vascular matrix metalloproteinase (MMP) system and their inhibitors (TIMPs) in human hypertension. The authors hypothesized that MMP-2, MMP-9, and TIMP-1 would be abnormal in hypertension, reflecting alterations in extracellular matrix (ECM) turnover. The authors measured plasma levels and activities of MMP-2, MMP-9, and TIMP-1 in 44 hypertensive patients and 44 controls. MMP-2 levels and activity were significantly higher in hypertensive group (p < .0001). Significant increase was also observed for MMP-9 level and activity (p < .0001) and for TIMP-1 (p < .0001) in hypertensive patients. Plasma levels and activities of MMP-2, MMP-9, and TIMP-1 are increased in hypertensive patients, which may reflect abnormal ECM metabolism. 相似文献