全文获取类型
收费全文 | 13922篇 |
免费 | 758篇 |
国内免费 | 92篇 |
专业分类
耳鼻咽喉 | 116篇 |
儿科学 | 335篇 |
妇产科学 | 249篇 |
基础医学 | 2008篇 |
口腔科学 | 362篇 |
临床医学 | 1206篇 |
内科学 | 3848篇 |
皮肤病学 | 245篇 |
神经病学 | 1266篇 |
特种医学 | 405篇 |
外科学 | 2008篇 |
综合类 | 43篇 |
一般理论 | 4篇 |
预防医学 | 660篇 |
眼科学 | 196篇 |
药学 | 764篇 |
中国医学 | 28篇 |
肿瘤学 | 1029篇 |
出版年
2023年 | 92篇 |
2022年 | 185篇 |
2021年 | 362篇 |
2020年 | 259篇 |
2019年 | 312篇 |
2018年 | 398篇 |
2017年 | 295篇 |
2016年 | 339篇 |
2015年 | 405篇 |
2014年 | 554篇 |
2013年 | 711篇 |
2012年 | 1136篇 |
2011年 | 1130篇 |
2010年 | 660篇 |
2009年 | 574篇 |
2008年 | 958篇 |
2007年 | 953篇 |
2006年 | 917篇 |
2005年 | 872篇 |
2004年 | 817篇 |
2003年 | 676篇 |
2002年 | 644篇 |
2001年 | 122篇 |
2000年 | 100篇 |
1999年 | 116篇 |
1998年 | 120篇 |
1997年 | 103篇 |
1996年 | 102篇 |
1995年 | 75篇 |
1994年 | 72篇 |
1993年 | 53篇 |
1992年 | 71篇 |
1991年 | 64篇 |
1990年 | 49篇 |
1989年 | 45篇 |
1988年 | 48篇 |
1987年 | 47篇 |
1986年 | 33篇 |
1985年 | 29篇 |
1984年 | 45篇 |
1983年 | 38篇 |
1982年 | 29篇 |
1981年 | 33篇 |
1980年 | 13篇 |
1979年 | 10篇 |
1978年 | 11篇 |
1977年 | 12篇 |
1976年 | 12篇 |
1975年 | 13篇 |
1974年 | 12篇 |
排序方式: 共有10000条查询结果,搜索用时 281 毫秒
61.
Tancredi M Sensi E Cipollini G Aretini P Lombardi G Di Cristofano C Presciuttini S Bevilacqua G Caligo MA 《European journal of human genetics : EJHG》2004,12(9):775-777
Germ-line mutations in the BRCA1 gene cause hereditary predisposition to breast and ovarian cancer. BRCA1 and BRCA2 mutations account for about 40% of high-risk families. Mutation-screening methods generally focus on genomic DNA and are usually PCR based; they enable the detection of sequence alterations such as point mutations and small deletions and insertions. However, they do not allow the detection of partial or entire exon(s) loss, because the presence of the homologous allele results in a positive PCR signal, giving rise to a false-negative result. Identification of unusual haplotypes in patient samples by an expectation maximization algorithm has recently been suggested as a method for identifying hemizygous regions caused by large intragenic deletions. Using a similar approach, we identified a novel BRCA1 genomic rearrangement in a breast/ovarian cancer family negative at the first mutation screening; we detected a deletion encompassing exons 14-19, probably due to replication slippage between Alu sequences. 相似文献
62.
63.
Impact of intranasal budesonide on immune inflammatory responses and epithelial remodeling in chronic upper airway inflammation 总被引:3,自引:0,他引:3
Mastruzzo C Greco LR Nakano K Nakano A Palermo F Pistorio MP Salinaro ET Jordana M Dolovich J Crimi DN Vancheri C 《The Journal of allergy and clinical immunology》2003,112(1):37-44
BACKGROUND: Histologic and immunohistologic features of nasal polyps (NP) are similar to those observed in asthma, thus suggesting a similar immunopathology. OBJECTIVE: The primary objective of this study was to further understand the anti-inflammatory and immunoregulatory effects of locally delivered corticosteroids. To this end, the effect of intranasal budesonide on the expression of specific cytokines, lymphocyte subsets, and epithelial remodeling in this model of airway tissue inflammation were studied. METHODS: We used immunohistochemical techniques to examine nasal mucosae (NM) from healthy individuals and nasal polyp (NP) tissues from patients with nasal polyposis obtained before and after intranasal budesonide treatment. RESULTS: First, the density of CD8(+) cells was markedly increased in NP tissues after intranasal budesonide treatment from 16.1 +/- 8.4 (M +/- SEM) per mm(2) to 39.9 +/- 24.1. Second, the density of cells immunoreactive for IL-4, IL-5, IFN-gamma, IL-12, and TGF-beta in NP was significantly greater than in control NM tissues. The density of IL-4(+) and IL-5(+) cells in NP tissues significantly decreased after budesonide treatment from 40 +/- 12 to 17.8 +/- 8 and from 19.3 +/- 11 to 10.4 +/- 7, respectively. In contrast, the density of IFN-gamma(+) and IL-12(+) cells remained unchanged. In addition, we found that the density of TGF-beta(+) cells significantly increased after intranasal budesonide from 18 +/- 5 to 41 +/- 9. Third, damage to the entire length of the NP epithelium was quantified using a grading system. The epithelium of untreated NP was substantially damaged; remarkable epithelial restitution with no apparent changes in stromal collagen deposition was observed after intranasal budesonide treatment. CONCLUSIONS: These findings demonstrate that intranasal budesonide induced an increase in CD8 population and a selective regulatory effect on tissue cytokine expression. Furthermore, intranasal budesonide promoted epithelial remodeling. We hypothesize that these immunoregulatory and remodeling effects elicited by steroids might be, at least in part, mediated by the induction of TGF-beta. 相似文献
64.
D'adda T Pizzi S Azzoni C Bottarelli L Crafa P Pasquali C Davoli C Corleto VD Delle Fave G Bordi C 《Human pathology》2002,33(3):322-329
Most foregut digestive endocrine neoplasms may be associated with the multiple endocrine type 1 (MEN-1) syndrome. In contrast, midgut/hindgut carcinoids never show such association. To investigate the pathogenetic involvement of the MEN-1 gene and of putative additional oncosuppressor gene(s) distal to it, a comparative analysis of loss of heterozygosity (LOH) at chromosome 11q13 to 11qter was performed in 27 foregut (pancreatic endocrine tumors [PETs]), 23 midgut (ileal and appendiceal), and 3 hindgut (rectal) endocrine tumors. LOH at the MEN-1 gene locus at 11q13 was observed in 52% of the 23 sporadic and in all 4 MEN-1-associated PETs and was found to consistently and continuously span to the most distal marker investigated at 11qter. In contrast, only occasional, discontinuous, and mostly interstitial LOH for 11q markers was observed in ileal (midgut) carcinoids, whereas no LOH was found in all appendiceal (midgut) and rectal (hindgut) carcinoids. The consistent extension of LOH from the MEN-1 region to 11qter in sporadic PETs suggests a mechanism of gene inactivation via chromosomal breakage and complete loss of chromosome 11q; furthermore, these results expand beyond the 11q13 region the search for additional oncosuppressor gene(s) potentially involved in the genesis of these neoplasms. The low frequency, limited extension, and discontinuous distribution of 11q deletions in midgut/hindgut carcinoids suggest that MEN-1 gene is not involved in the pathogenesis of these tumors. 相似文献
65.
Licastro F Grimaldi LM Bonafè M Martina C Olivieri F Cavallone L Giovanietti S Masliah E Franceschi C 《Neurobiology of aging》2003,24(7):921-926
Two different polymorphic regions of the interleukin-6 (IL-6) gene were investigated in patients with Alzheimer's disease (AD) and non-demented controls. The -174 C allele in the promoter region of IL-6 gene was over-represented in AD patients compared to controls and significantly increased the risk of AD. Moreover, the -174 CC genotype was associated with a high risk of the disease in women. The D allele of a variable number of tandem repeat (VNTR) was in strong linkage disequilibrium with the -174 C allele and slightly increased AD risk. On the other hand, the frequency of the VNTR C allele was decreased in patients with AD and was negatively associated with the risk of developing AD. Both the -174 CC and VNTR DD genotypes were also associated with increased IL-6 levels in the blood and brain from AD. These findings suggest that IL-6 may play a multifaceted role in AD by affecting the turnover of the cytokine. 相似文献
66.
Claudio Oliveira Fausto Foresti Marcos Guilherme Rigolino Yara Aiko Tabata 《Chromosome research》1995,3(3):182-190
The surface-spreading synaptonemal complex (SC) technique was employed to analyze spermatocytes and oocytes of rainbow trout in order to visualize the process of autosome and sex chromosome synapsis in this species. The structure of lateral elements (LEs) of the SC and the chromosome synapsis process at the stages of leptotene, zygotene and pachytene are described. Comparative analysis of SCs of spermatocytes and oocytes showed a difference in the synaptic process, i.e. in spermatocytes all LEs were synapsed before the appearance of centromeric regions in the biarmed elements, while in the oocytes some fully synapsed LEs, including the centromeric region of the biarmed elements, were found together with fully or partially unsynapsed LEs. In males the sex chromosome synapsis starts only after all autosomes have synapsed. Irregular synapses involving three or four LEs were found in 3.4% of the cells analyzed in mid or late zygotene. Multivalents were found in males and females. Some aspects of initial meiotic development and their implications in rainbow trout cytogenetics, genetics and evolution are discussed. 相似文献
67.
Comparison of LCx with other current viral load assays for detecting and quantifying human immunodeficiency virus type 1 RNA in patients infected with the circulating recombinant form A/G (CRF02) 下载免费PDF全文
Amendola A Bordi L Angeletti C Girardi E Ippolito G Capobianchi MR 《Journal of clinical microbiology》2004,42(2):811-815
LCx was compared to other assays in measuring human immunodeficiency virus type 1 (HIV-1) CRF02 viremia. LCx showed significant but low correlation with the other methods. Values of <2.60 log(10) cp/ml were observed in 29.6% of specimens with LCx and in only 14.8% with bDNA and PCR, suggesting suboptimal performance of LCx with CRF02. 相似文献
68.
A new one-step computational procedure is presented for estimating the parameters of the nonlinear three-element windkessel
model of the arterial system incorporating a pressure-dependent compliance. The data required are pulsatile aortic pressure
and flow. The basic assumptions are a steadystate periodic regime and a purely elastic compliant element. By stating two conditions,
zero mean flow and zero mean power in the compliant element, peripheral and characteristic resistances are determined through
simple closed form formulas as functions of mean values of the square of aortic pressure, the square of aortic flow, and the
product of aortic pressure with aortic flow. The pressure across as well as the flow through the compliant element can be
then obtained so allowing the calculation of volume variation and compliance as functions of pressure. The feasibility of
this method is studied by applying it to both simulated and experimental data relative to different circulatory conditions
and comparing the results with those obtained by an iterative parameter optimization algorithm and with the actual values
when available. The conclusion is that the proposed method appears to be effective in identifying the three-element windkessel
even in the case of nonlinear compliance. 相似文献
69.
Impaired hair follicle morphogenesis and cycling with abnormal epidermal differentiation in nackt mice,a cathepsin L-deficient mutation 总被引:1,自引:0,他引:1 下载免费PDF全文
Benavides F Starost MF Flores M Gimenez-Conti IB Guénet JL Conti CJ 《The American journal of pathology》2002,161(2):693-703
We previously described an autosomal-recessive mutation named nackt (nkt) exhibiting partial alopecia associated with CD4(+) T-cell deficiency. Also, we recently reported that nkt (now Ctsl(nkt)) comprises a deletion in the cathepsin L (Ctsl) gene. Another recent study reported that Ctsl knockout mice have CD4(+) T-cell deficiency and periodic shedding of hair, which recapitulate the nkt mutation and the old furless (fs) mutation. The current study focuses on the dermatological aspects of the nkt mutation. Careful histological analysis of skin development of homozygous nkt mice revealed a delayed hair follicle morphogenesis and late onset of the first catagen stage. The skin of Ctsl(nkt)/Ctsl(nkt) mice showed mild epidermal hyperplasia and hyperkeratosis, severe hyperplasia of the sebaceous glands, and structural alterations of hair follicles. Epidermal differentiation seems to be affected in nkt skin, with overexpression of involucrin and profilaggrin/filaggrin along with focal areas of keratin 6 expression in the interfollicular epidermis. Severe epidermal hyperplasia, acanthosis, orthokeratosis, and hyperkeratosis were only observed in mice maintained in nonpathogen-free environments. The analysis of Rag2-/- Ctsl(nkt)/Ctsl(nkt) double-mutant mice indicates that the skin defect remains under the absence of T and B cells. This animal model provides in vivo evidence that cysteine protease cathepsin L plays a critical role in hair follicle morphogenesis and cycling, as well as epidermal differentiation. 相似文献
70.
Use of 16S rRNA gene sequencing for rapid identification and differentiation of Burkholderia pseudomallei and B. mallei 下载免费PDF全文
Gee JE Sacchi CT Glass MB De BK Weyant RS Levett PN Whitney AM Hoffmaster AR Popovic T 《Journal of clinical microbiology》2003,41(10):4647-4654
Burkholderia pseudomallei and B. mallei, the causative agents of melioidosis and glanders, respectively, are designated category B biothreat agents. Current methods for identifying these organisms rely on their phenotypic characteristics and an extensive set of biochemical reactions. We evaluated the use of 16S rRNA gene sequencing to rapidly identify these two species and differentiate them from each other as well as from closely related species and genera such as Pandoraea spp., Ralstonia spp., Burkholderia gladioli, Burkholderia cepacia, Burkholderia thailandensis, and Pseudomonas aeruginosa. We sequenced the 1.5-kb 16S rRNA gene of 56 B. pseudomallei and 23 B. mallei isolates selected to represent a wide range of temporal, geographic, and origin diversity. Among all 79 isolates, a total of 11 16S types were found based on eight positions of difference. Nine 16S types were identified in B. pseudomallei isolates based on six positions of difference, with differences ranging from 0.5 to 1.5 bp. Twenty-two of 23 B. mallei isolates showed 16S rRNA gene sequence identity and were designated 16S type 10, whereas the remaining isolate was designated type 11. This report provides a basis for rapidly identifying and differentiating B. pseudomallei and B. mallei by molecular methods. 相似文献