全文获取类型
收费全文 | 1494篇 |
免费 | 95篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 47篇 |
妇产科学 | 8篇 |
基础医学 | 265篇 |
口腔科学 | 26篇 |
临床医学 | 95篇 |
内科学 | 214篇 |
皮肤病学 | 218篇 |
神经病学 | 137篇 |
特种医学 | 64篇 |
外科学 | 275篇 |
综合类 | 8篇 |
预防医学 | 71篇 |
眼科学 | 21篇 |
药学 | 51篇 |
中国医学 | 1篇 |
肿瘤学 | 84篇 |
出版年
2022年 | 5篇 |
2021年 | 3篇 |
2020年 | 4篇 |
2019年 | 7篇 |
2018年 | 10篇 |
2017年 | 9篇 |
2016年 | 12篇 |
2015年 | 30篇 |
2014年 | 36篇 |
2013年 | 29篇 |
2012年 | 116篇 |
2011年 | 103篇 |
2010年 | 55篇 |
2009年 | 37篇 |
2008年 | 122篇 |
2007年 | 115篇 |
2006年 | 123篇 |
2005年 | 92篇 |
2004年 | 108篇 |
2003年 | 137篇 |
2002年 | 101篇 |
2001年 | 36篇 |
2000年 | 25篇 |
1999年 | 31篇 |
1998年 | 18篇 |
1997年 | 19篇 |
1996年 | 18篇 |
1995年 | 10篇 |
1994年 | 8篇 |
1993年 | 12篇 |
1992年 | 6篇 |
1991年 | 10篇 |
1990年 | 10篇 |
1989年 | 7篇 |
1988年 | 10篇 |
1987年 | 17篇 |
1986年 | 6篇 |
1985年 | 7篇 |
1984年 | 7篇 |
1983年 | 5篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1979年 | 5篇 |
1976年 | 4篇 |
1973年 | 4篇 |
1968年 | 3篇 |
1967年 | 5篇 |
1964年 | 5篇 |
1925年 | 4篇 |
1922年 | 3篇 |
排序方式: 共有1590条查询结果,搜索用时 15 毫秒
1.
2.
PD Dr. M. Frosch 《Monatsschrift für Kinderheilkunde》2006,154(9):880-885
Wegener’s granulomatosis (WG) is a necrotising granulomatous small vessel vasculitis with a clinical predilection for the involvement of the upper airways, lungs and kidneys. It occurs at all ages. The pathogenesis of WG is determined by the pathological activation of phagocytes during transmigration through the vessel. Whereas most aspects of WG are similar at all ages, some features appear to be significantly different. WG in childhood is more frequently complicated by subglottic stenosis and nasal deformity, while treatment related morbidity is less common compared to adults. The introduction of combined treatment with cyclophosphamide and glucocorticoids has resulted in a dramatic improvement in patient outcome; however, commonly occurring disease relapses and the risk of chronic organ damage at all ages make long-term follow-up of all patients necessary. 相似文献
3.
Beta amyloid is focally deposited within the outer basement membrane in the amyloid angiopathy of Alzheimer''s disease. An immunoelectron microscopic study. 总被引:2,自引:0,他引:2
下载免费PDF全文
![点击此处可从《The American journal of pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
H. Yamaguchi T. Yamazaki C. A. Lemere M. P. Frosch D. J. Selkoe 《The American journal of pathology》1992,141(1):249-259
The fine structure of cerebral amyloid angiopathy, especially in small and presumably early deposits, was examined by immunolabeling of the beta/A4 protein in semithin and ultrathin sections from brains with Alzheimer's disease. The following findings emerged: 1) in large leptomeningeal arteries, small, focal amyloid deposits appear to consist of clusters of delicate (approximately 8 nm diameter) amyloid fibrils, not previously described, in the outermost part of the basement membrane (BM) at the media-adventitia junction; 2) in small leptomeningeal arteries and perforating cortical arterioles, small foci of delicate amyloid fibrils were observed within the BM. They appeared mostly in the outer portion of the BM, around intact smooth muscle cells, rather than in the subendothelial region. In larger and presumably more advanced deposits, coarse amyloid fibrils (approximately 10 nm) occupied the abluminal BM, and adjacent smooth muscle cells showed degeneration; and 3) in capillaries, small amounts of delicate (approximately 8 nm) amyloid fibrils, not previously described, were seen within the BM in the smallest discernible deposits. The BM at these sites was abnormally folded and layered. In larger deposits, amyloid fibrils appeared to extravasate from the outer BM of the capillary into the neuropil and were surrounded by astrocytic foot processes and/or microglia. Our results suggest that vascular amyloid fibrils may first be formed within the abluminal vascular BM, that is, outside of cells. The BM may trap degradative intermediates of the amyloid precursor protein that contain the beta/A4 region, and local proteases may then cleave them further to yield amyloidogenic fragments. 相似文献
4.
5.
Cloning and sequencing of the genes coding for the 10- and 60-kDa heat shock proteins from Pseudomonas aeruginosa and mapping of a species-specific epitope.
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
A genomic library of Pseudomonas aeruginosa DNA was screened with a monoclonal antibody (MAb 2528) specific for the P. aeruginosa 60-kDa heat shock protein. A positive clone, pAS-1, was isolated. The gene coding for P. aeruginosa chaperonin (hsp60) was localized to a 2-kb EcoRI fragment subcloned in pAS-2. A sequence analysis of pAS-2 and parts of pAS-1 identified two open reading frames that encoded proteins with calculated molecular masses of 10 and 57 kDa. In amino acid sequence comparison studies the sequences of these proteins, which were designated GroES and GroEL, exhibited up to 78% homology with known prokaryotic sequences of 10- and 60-kDa heat shock proteins (hsp10 and hsp60). In order to map the epitope recognized by MAb 2528, a series of GroEL nested carboxy-terminal deletion clones were tested with MAb 2528. We identified the clone with the shortest insertion that was still recognized by MAb 2528 and the clone with the largest insertion that was not recognized by MAb 2528. The 3' ends of the insertions were determined by sequencing and were found to delimit a region that encoded 25 amino acid residues. Synthetic oligonucleotides that coded for peptides possibly resembling the epitope within this region were ligated into expression vector pGEX-3X, and fusion proteins expressed by these clones were tested for reactivity with MAb 2528. By using this method we determined that the decapeptide QADIEARVLQ (positions 339 to 348 on GroEL) was responsible for the binding of P. aeruginosa-specific MAb 2528. 相似文献
6.
The shufflon of Salmonella enterica serovar Typhi regulates type IVB pilus-mediated bacterial self-association
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Previously, it was shown that type IVB pili encoded by the Salmonella enterica serovar Typhi pil operon are used to facilitate bacterial entry into human intestinal epithelial cells in vitro and that such entry is inhibited by purified prepilin (pre-PilS) protein (X.-L. Zhang, I. S. M. Tsui, C. M. C. Yip, A. W. Y. Fung, D. K.-H. Wong, X. Dai, Y. Yang, J. Hackett, and C. Morris, Infect. Immun. 68:3067-3073, 2000). The pil operon concludes with a simple shufflon, and a recombinase gene product (Rci) inverts DNA in the C-terminal region of the pilV gene to allow synthesis of two distinct PilV proteins, PilV1 and PilV2, which are presumptive minor pilus proteins. We show here that the type IVB pili mediate bacterial self-association, but only when the PilV1 and PilV2 proteins are not expressed. This may be achieved in wild-type serovar Typhi by rapid DNA inversion activity of the shufflon. We show that the inversion activity inhibits the expression of genes inserted between the 19-bp inverted repeats used for Rci-mediated recombination and that the activity of Rci increases when DNA is supercoiled. The data suggest that serovar Typhi self-associates under conditions (such as low oxygen tension in the gut) that favor DNA supercoiling. These results explain (i) the function of the serovar Typhi shufflon and (ii) why there are only two possible shufflon states, in contrast to the many possible states of other shufflon systems. The data further indicate that a very early step in serovar Typhi pathogenesis may be type IVB pilus-mediated self-association of bacteria in the anaerobic human small intestine prior to invasion of the human gut epithelium. The suggested type IVB pilus-dependent step in typhoid fever pathogenesis may partially explain the enhanced invasiveness of serovar Typhi for humans. 相似文献
7.
M B Podlisny D T Stephenson M P Frosch I Lieberburg J A Clemens D J Selkoe 《Neurobiology of aging》1992,13(5):561-567
Because progressive amyloid beta-protein (A beta P) deposition and surrounding neuritic dystrophy occur spontaneously in primates, we evaluated the in vivo effects of synthetic A beta P in monkey cortex. Experimental and control A beta P were stereotactically injected into multiple neocortical sites of adult rhesus monkeys in a vehicle of either artificial cerebrospinal fluid or acetonitrile. After 2 weeks or 3 months, injection sites were identified and characterized histologically and immunocytochemically. A beta P antibodies specifically detected the injected A beta P1-40 peptide. Serial sections stained with silver and antineurofilament protein demonstrated comparable degrees of degenerating neurons, dystrophic neurites, and axonal spheroids associated with both experimental and control peptide injections. Alz 50 staining was sparse or absent in all sites. We conclude that specific cellular changes closely resembling AD pathology were not detected in these experiments, and that control and experimental A beta P peptides produced indistinguishable effects. Methodological concerns regarding the in vivo modeling of A beta P bioactivity are discussed. 相似文献
8.
Parkin localizes to the Lewy bodies of Parkinson disease and dementia with Lewy bodies 总被引:31,自引:0,他引:31
下载免费PDF全文
![点击此处可从《The American journal of pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Schlossmacher MG Frosch MP Gai WP Medina M Sharma N Forno L Ochiishi T Shimura H Sharon R Hattori N Langston JW Mizuno Y Hyman BT Selkoe DJ Kosik KS 《The American journal of pathology》2002,160(5):1655-1667
Mutations in alpha-synuclein (alpha S) and parkin cause heritable forms of Parkinson disease (PD). We hypothesized that neuronal parkin, a known E3 ubiquitin ligase, facilitates the formation of Lewy bodies (LBs), a pathological hallmark of PD. Here, we report that affinity-purified parkin antibodies labeled classical LBs in substantia nigra sections from four related human disorders: sporadic PD, inherited alphaS-linked PD, dementia with LBs (DLB), and LB-positive, parkin-linked PD. Anti-parkin antibodies also detected LBs in entorhinal and cingulate cortices from DLB brain and alphaS inclusions in sympathetic gangliocytes from sporadic PD. Double labeling with confocal microscopy of DLB midbrain sections revealed that approximately 90% of anti-alpha S-reactive LBs were also detected by a parkin antibody to amino acids 342 to 353. Accordingly, parkin proteins, including the 53-kd mature isoform, were present in affinity-isolated LBs from DLB cortex. Fluorescence resonance energy transfer and immunoelectron microscopy showed that alphaS and parkin co-localized within brainstem and cortical LBs. Biochemically, parkin appeared most enriched in cytosolic and postsynaptic fractions of adult rat brain, but also in purified, alpha S-rich presynaptic elements that additionally contained parkin's E2-binding partner, UbcH7. We conclude that parkin and UbcH7 are present with alphaS in subcellular compartments of normal brain and that parkin frequently co-localizes with alpha S aggregates in the characteristic LB inclusions of PD and DLB. These results suggest that functional parkin proteins may be required during LB formation. 相似文献
9.
Cell culture-based transdominant genetic techniques provide new methods for discovering peptide/RNA modulators of cellular pathways. We applied this technology to isolate a peptide inhibitor of human rhinovirus. A green fluorescent protein (GFP)-scaffolded library of cDNA fragments was expressed in HeLa cells from a retroviral vector and screened for inhibitors of rhinovirus-mediated cell killing. A DNA clone, I421, increased cell survival in an HRV14 challenge assay from less than 0.5% to greater than 60%. It encodes a 53-amino-acid C-terminal extension of the GFP scaffold. Particular subclones of Hela cells expressing I421 (exemplified by I421dp3) show a delay in virus production and a 50-fold decrease in viral RNA levels at 6-8 h postinfection. HRV2, HRV14, and HRV16 show a dramatic decrease in plaque-forming ability on I421dp3 while Coxsackievirus B3 showed a small reduction. Levels of ICAM-1, the receptor for the main rhinovirus serotype, are not altered in I421dp3. 相似文献
10.
Faller G Berndt R Borchard F Ell C Fuchs KH Geddert H Gossner L Günther T Kirchner T Koch HK Langner C Lüttges J May A Müller S Oberhuber G Seitz G Stolte M Tannapfel A Vieth M Walch A Rüschoff J;Working Group for Gastroenterological Pathology German Society for Pathology 《Der Pathologe》2003,24(1):9-14
There are a number of difficulties regarding the diagnosis of Barrett's mucosa and the varying grades of neoplasia that may be associated with it. It was therefore the aim of a consensus conference of the "Working Group for Gastroenterological Pathology within the German Society of Pathology" to achieve standardization regarding the following issues: definition and diagnostic criteria for Barrett's mucosa and its discrimination from intestinal metaplasia of the cardia, diagnostic criteria for intraepithelial neoplasia, number of biopsies necessary to establish the diagnosis, significance of additional immunohistochemical and/or molecular biological methods as well as importance of a second opinion in the diagnosis of intraepithelial neoplasia. 相似文献