全文获取类型
收费全文 | 108篇 |
免费 | 4篇 |
专业分类
儿科学 | 1篇 |
妇产科学 | 3篇 |
基础医学 | 35篇 |
临床医学 | 11篇 |
内科学 | 13篇 |
神经病学 | 13篇 |
特种医学 | 2篇 |
外科学 | 11篇 |
预防医学 | 2篇 |
眼科学 | 1篇 |
药学 | 11篇 |
肿瘤学 | 9篇 |
出版年
2022年 | 1篇 |
2021年 | 4篇 |
2020年 | 3篇 |
2019年 | 6篇 |
2018年 | 4篇 |
2017年 | 2篇 |
2016年 | 1篇 |
2015年 | 5篇 |
2014年 | 6篇 |
2013年 | 6篇 |
2012年 | 8篇 |
2011年 | 7篇 |
2010年 | 3篇 |
2009年 | 3篇 |
2008年 | 4篇 |
2007年 | 5篇 |
2006年 | 7篇 |
2005年 | 7篇 |
2004年 | 2篇 |
2003年 | 8篇 |
2002年 | 1篇 |
2001年 | 5篇 |
2000年 | 2篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1932年 | 1篇 |
排序方式: 共有112条查询结果,搜索用时 31 毫秒
51.
Search for mutations involved in human globozoospermia 总被引:4,自引:0,他引:4
Pirrello O Machev N Schimdt F Terriou P Ménézo Y Viville S 《Human reproduction (Oxford, England)》2005,20(5):1314-1318
BACKGROUND: Globozoospermia is a severe form of teratozoospermia characterized by round-headed sperm with an absence of acrosomes. Family cases of globozoopermia suggest that this pathology has genetic origins, but the mode of inheritance remains unknown. So far, no responsible genes have been identified. Recently, a mouse lacking the casein kinase IIalpha' (encoded by the Csnk2a2 gene) was described. This mutant mouse presents a single phenotype reminiscent of that seen in human globozoospermia. Interestingly, the fission yeast orthologue (orb5) exhibits, when mutated, a spherical phenotype. Casein kinase II is a heterotetramer, composed of two catalytic subunits alpha or alpha' and two regulatory beta subunits (encoded by the Csnk2b gene). METHODS and RESULTS: Based on the evolution conservation, phenotypes observed in mouse and yeast mutant and the structure of casein kinase II, we analysed Csnk2a2 and Csnk2b genes in six patients with globozoospermia and 10 fertile controls. Genomic DNA was extracted from peripheral blood and PCR was performed to amplify Csnk2a2 and Csnk2b genes before sequencing. CONCLUSION: No mutation was identified among these six patients. Further work is needed, with a larger patient data set, to identify putative genes involved in this form of male infertility. 相似文献
52.
Alkoxyalkyl esters of cidofovir, an acyclic nucleoside phosphonate, have been shown to have antiviral activities several orders of magnitude greater than unmodified cidofovir against cytomegalovirus, herpes simplex virus, vaccinia, cowpox, ectromelia and adenoviruses in vitro. Hexadecyloxypropyl-cidofovir is orally bioavailable and active in lethal animal models of vaccinia, cowpox, ectromelia and cytomegalovirus. To see if this strategy is also applicable to other acyclic nucleoside phosphonates, we have converted several phosophonomethoxyethyl purines and pyrimidines to their hexadecyloxypropyl, octadecyloxyethyl and oleyloxyethyl esters and compared their activity against HIV-1 with the activity of the respective unmodified acyclic nucleoside phosphonates. The hexadecyloxypropyl esters of phosphonomethoxyethyl-adenine, phosphonomethoxyethyl-2,6-diaminopurine and phosphonomethoxyethyl-N(6)-cyclopropyl-diaminopurine were 3-5 orders of magnitude more active against HIV-1 in vitro than the parent nucleotides. The EC(50) values for these compounds were in the 10-20 pM range with selective indexes of 1,250 to >4,000. The acyclic pyrimidine phosphonates were generally inactive against HIV-1 in vitro. Phosphonomethoxyethyl-cytosine and phosphonomethoxyethyl-5-fluorocytosine were inactive against HIV-1. Surprisingly, hexadecyloxypropyl-phosphonomethoxyethyl-5-fluorocytosine was active against HIV-1 with a submicromolar EC(50) and a selective index of 174. Esterification of acyclic nucleoside phosphonates with alkoxyalkyl moieties may represent a general approach for increasing antiviral activity and selectivity of this class of antivirals. 相似文献
53.
Nadejda Stoewa 《Naunyn-Schmiedeberg's archives of pharmacology》1932,166(1):15-21
Ohne ZusammenfassungMit 1 Textabbildung.Das für die Untersuchung notwendige Stickoxydul wurde mir in liebenswürdiger Weise von der Firma I. G. Farbenindustrie Abt. Höchst kostenlos zur Verfügung gestellt, wofür ihr hierdurch aufs beste gedankt sei. 相似文献
54.
Meyer dos Santos S Klinkhardt U Scholich K Nelson K Monsefi N Deckmyn H Kuczka K Zorn A Harder S 《Blood》2011,117(18):4999-5008
The membrane-anchored CX3C chemokine fractalkine (FKN) is expressed on activated endothelium and is associated with the development of atherosclerosis. The potential of FKN in mediating platelet adhesion beyond platelet activation remains unexplored to date. A flow-based adhesion assay was used to study the adhesion of platelets to immobilized FKN under physiologic flow conditions. Platelet adhesion to von Willebrand factor (VWF) was increased in the presence of FKN at 600 inverse seconds. Additional platelet adhesion to FKN coimmobilized with VWF was dependent on the FKN receptor CX3CR1 and activation of glycoprotein (GP) IIb/IIIa. The number of platelets rolling on VWF was likewise enhanced in the presence of FKN. The enhancement of rolling on FKN and VWF was insensitive to anti-CX3CR1 antibody but was fully inhibited by neutralizing GPIbα function. The extracellular domain of GPIbα was covalently coupled to fluorescent microspheres, and microsphere binding was significantly higher in the presence of FKN. Platelet adhesion to activated endothelium in vitro and to intact human arteries was substantially increased in an FKN-dependent manner. These data demonstrate that endothelial expressed FKN activates platelets via its cognate receptor CX3CR1, whereas platelet adhesion is predominantly mediated by GPIbα and independent of CX3CR1. 相似文献
55.
56.
Mycobacterial Hsp65-IgG-expressing tolerogenic B cells confer protection against adjuvant-induced arthritis in Lewis rats 总被引:2,自引:0,他引:2
OBJECTIVE: Tolerization of T cells directed against a target autoantigen is a desired goal of experimental approaches for the treatment of autoimmune diseases, and novel and improved methods of tolerance induction are continuously being sought. Because most traditional methods of tolerance induction using soluble antigen are effective in the prevention of autoimmunity but fail to control established disease, this study was carried out to explore an innovative tolerogenic approach for the treatment of ongoing disease, using the rat adjuvant-induced arthritis (AIA) model of human rheumatoid arthritis. METHODS: Lewis (RT.1(l)) rats were injected subcutaneously with heat-killed Mycobacterium tuberculosis H37Ra to induce AIA. Before or after AIA induction, Lewis rats were treated intraperitoneally (IP) with tolerogenic B cells expressing a fusion construct of mycobacterial 65-kd heat-shock protein (Hsp65) and IgG heavy-chain. For comparison, control rats were treated IP with ovalbumin (OVA)-IgG-expressing B cells or soluble mycobacterial Hsp65, and the effects on AIA were observed. We also tested the immune response to mycobacterial Hsp65 in B cell-tolerized rats. RESULTS: Administration of tolerogenic mycobacterial Hsp65-expressing B cells as well as soluble mycobacterial Hsp65, but not OVA-expressing B cells, resulted in a significant decrease in the severity of subsequent AIA. However, in rats with established disease, only the B cell regimen of mycobacterial Hsp65, but not the soluble antigen, suppressed ongoing AIA. CONCLUSION: Mycobacterial Hsp65-IgG-expressing B cells can successfully attenuate the progression of AIA. This study introduces a promising approach for the treatment of arthritis that should be further explored. 相似文献
57.
Weber S Bernhard D Lukowski R Weinmeister P Wörner R Wegener JW Valtcheva N Feil S Schlossmann J Hofmann F Feil R 《Circulation research》2007,101(11):1096-1103
Smooth muscle expresses the Ialpha and the Ibeta isoforms of cGMP-dependent protein kinase I (cGKI). Inactivation of the murine cGKI gene prkg1 leads to multiple phenotypes and premature death at approximately 6 weeks. We reconstituted mice with the cGKIalpha or -Ibeta isozyme to test which isozyme was needed to support basic smooth muscle functions. Mice were generated by gene targeting. The cGKIalpha or the -Ibeta coding sequences were placed under the control of the SM22alpha promoter to express either isoform selectively in smooth muscle cells (SM-Ialpha or SM-Ibeta transgene). To generate smooth muscle-specific cGKIalpha or cGKIbeta rescue mice, the SM-Ialpha or SM-Ibeta transgenes were crossed on a cGKI-/- genetic background. The levels of cGKIalpha or -Ibeta expression were comparable to endogenous cGKI expression in wild-type aortic and intestinal smooth muscles. In cGKIalpha or -Ibeta rescue mice, expression of the isozymes was not detectable in non-smooth muscle tissues and cells. Median survival time of the Ialpha and Ibeta rescue mice was 52 weeks. Both isozymes mediated the 8-bromo-cGMP-induced relaxation of precontracted jejunum and aorta muscle strips. Activation of both isozymes reduced hormone- or K+-induced [Ca2+]i levels. The cGKIalpha and cGKIbeta rescue mice did not show a significant difference in intestinal passage time of BaSO4 in comparison with wild-type animals. Telemetric blood pressure measurements in conscious freely moving animals did not show differences between rescues and control mice in basal blood pressure and its regulation by DETA-NO, sodium nitroprusside, carbachol, or Y-27632. These results show that cGKI in smooth muscle is essential and that either cGKI isozyme alone can rescue basic vascular and intestinal smooth muscle functions. 相似文献
58.
E. V. Loseva V. N. Vorob''ev T. G. Alekseeva I. V. Ermakova I. S. Zakharov N. N. Lermontova P. M. Balaban 《Bulletin of experimental biology and medicine》2001,132(1):689-694
Survival of neuronal ganglia from newborn snail (Helix aspera L.) in the brain of adult rats was studied. Snail ganglion survived in the brain of warm-blooded animals for 6 months without inducing immune conflict. At early stages (5 days) after transplantation, xenografts increased in size and were several times larger than native ganglia from 10-day-old snails, thereafter (on days 28 and 180) they became smaller still surpassing the sizes of ganglia from snail of the corresponding age. Rapid enlargement of the xenograft was due to cell reactive processes in the ganglion. Deep penetration of large vessels from xenografts to rat brain was observed. 相似文献
59.
60.
Nadejda Monsefi Andreas Zierer Mahmud Khalil Mahmut Ay Andres Beiras-Fernandez Anton Moritz Ulrich Alfred Stock 《Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital》2014,41(6):609-612
The MitraClip percutaneous mitral valve repair system, developed as an option for percutaneous mitral repair, was clinically introduced in 2007. From 2010 through 2012, 6 of our patients underwent mitral valve surgery after MitraClip failure. Their mean age was 75 ± 7.7 years (range, 62–87 yr). Three had undergone cardiac surgery previously. In 5 of the 6 patients, mitral regurgitation recurred after initially successful MitraClip deployment and was the indication for surgery. The mean interval between MitraClip implantation and surgery was 106 ± 86 days (range, 0–238 d).Mitral valve repair was feasible in 3 patients; the others underwent valve replacement. All the patients underwent additional cardiac procedures, because the MitraClip worsened existing conditions. Echocardiograms revealed sufficient valvular repairs. Two patients died during hospitalization, one of cerebral infarction and the other of bowel ischemia.Mitral valve repair after failed MitraClip therapy can be complex and a surgical challenge. Careful consideration should be given to appropriate patient selection for MitraClip therapy, because the MitraClip can cause existing pathologic valvular conditions to deteriorate substantially. The interval between MitraClip failure and corrective surgery should be as short as possible. The primary indication is an issue of ongoing discussion. 相似文献