全文获取类型
收费全文 | 7100篇 |
免费 | 391篇 |
国内免费 | 31篇 |
专业分类
耳鼻咽喉 | 33篇 |
儿科学 | 310篇 |
妇产科学 | 91篇 |
基础医学 | 1191篇 |
口腔科学 | 59篇 |
临床医学 | 610篇 |
内科学 | 1258篇 |
皮肤病学 | 152篇 |
神经病学 | 751篇 |
特种医学 | 377篇 |
外科学 | 1126篇 |
综合类 | 20篇 |
一般理论 | 1篇 |
预防医学 | 241篇 |
眼科学 | 100篇 |
药学 | 504篇 |
中国医学 | 15篇 |
肿瘤学 | 683篇 |
出版年
2023年 | 29篇 |
2022年 | 59篇 |
2021年 | 92篇 |
2020年 | 75篇 |
2019年 | 105篇 |
2018年 | 130篇 |
2017年 | 124篇 |
2016年 | 162篇 |
2015年 | 162篇 |
2014年 | 218篇 |
2013年 | 283篇 |
2012年 | 389篇 |
2011年 | 472篇 |
2010年 | 281篇 |
2009年 | 294篇 |
2008年 | 466篇 |
2007年 | 498篇 |
2006年 | 468篇 |
2005年 | 498篇 |
2004年 | 479篇 |
2003年 | 483篇 |
2002年 | 426篇 |
2001年 | 128篇 |
2000年 | 82篇 |
1999年 | 105篇 |
1998年 | 110篇 |
1997年 | 78篇 |
1996年 | 68篇 |
1995年 | 60篇 |
1994年 | 54篇 |
1993年 | 55篇 |
1992年 | 47篇 |
1991年 | 39篇 |
1990年 | 34篇 |
1989年 | 33篇 |
1988年 | 39篇 |
1987年 | 20篇 |
1986年 | 17篇 |
1985年 | 31篇 |
1984年 | 22篇 |
1983年 | 19篇 |
1982年 | 24篇 |
1981年 | 27篇 |
1980年 | 24篇 |
1979年 | 22篇 |
1978年 | 26篇 |
1977年 | 23篇 |
1976年 | 28篇 |
1975年 | 15篇 |
1973年 | 18篇 |
排序方式: 共有7522条查询结果,搜索用时 31 毫秒
61.
Johannes Hartmann Volker Maaßen Peter Rieber Harald Fricke 《European journal of immunology》1995,25(9):2626-2631
62.
BACKGROUND: Immunization of mice with low doses of protein antigens like keyhole limpet hemocyanin (KLH) results in high immunoglobulin (Ig) E Ab titers in the sera of those mice while the application of high doses leads to the production of only marginal amounts of IgE but high levels of IgG2a and IgG1 antibodies. The aim of these studies is to elucidate the role of interleukin-10 (IL-10) in the generation of memory T cells and their contribution to the production of IgE Ab. METHODS: Both IL-10-deficient mice and control mice were immunized repeatedly with KLH. Serum levels of KLH-specific Ab were measured. The frequencies of memory T cells were determined by flow cytometry and the role of CD4+ and CD8+ T cells was evaluated. RESULTS: IL-10-deficient mice show an augmented production of IgE in vivo. They exhibit enhanced ratios of CD4+:CD8+ memory T cells with a CD44+, CD62L- phenotype with a significantly raised generation of CD4+ memory T cells. On the other hand, the development of CD8+ memory T cells is reduced moderately in IL-10-deficient mice, which is an interesting fact since it has been shown that primed CD8+ T cells suppress IgE Ab production at least in vitro. The ratios of total CD4+:CD8+ T cells are augmented in IL-10-deficient mice compared to wild-type mice and in K01 mice compared to K100 mice in vivo. CONCLUSIONS: The elevated ratios of CD4+:CD8+ T cells indicate a higher capacity to provide B cell help, which results in a strongly elevated IgE response in IL-10-deficient mice. These altered ratios are furthermore interesting in view of the regulatory role of CD8+ T cells which provide a suppressive potential regarding IgE Ab production as shown in vitro. The capacity of IL-10 to suppress IgE Ab production by reduction of the CD4+:CD8+ memory T cell ratio opens new possibilities in the interference with allergic disorders. 相似文献
63.
Weigmann HJ Jacobi U Antoniou C Tsikrikas GN Wendel V Rapp C Gers-Barlag H Sterry W Lademann J 《Journal of biomedical optics》2005,10(1):14009
Penetration profiles of topically applied drugs and cosmetic products provide important information on their efficacy. The application of tape stripping in combination with UV/VIS spectroscopy is checked to determine the local position of topically applied substances inside the stratum corneum, the penetration profile. The amount of corneocytes removed with each tape strip is quantified via the particle-dependent absorption, the pseudoabsorption, in the visible spectral range. The concentration of a typical UV filter substance, 4-methylbenzylidene camphor, is determined by optical spectroscopy using the tape strips removed originally. In this case, a time-dependent increase in the absorbance must be taken into account. Laser scanning microscopic investigations confirm that the nonhomogeneous distribution of the filter substance, on the strips, can explain this spectroscopic behavior. When reaching a homogeneous distribution, the UV spectroscopic signal reflects the correct concentration. These spectroscopic values are compared with high performance liquid chromatography (HPLC) data. The values obtained with both methods for the concentrations of 4-methylbenzylidene camphor are in good agreement. The data obtained are used to illustrate the determination of a penetration profile of a UV filter substance. The results demonstrate that the described protocol is well suited to characterize, in a simple manner, topically applied substances that have a characteristic UV/VIS absorption band. 相似文献
64.
Ribosomal RNA of Nosema algerae and phylogenetic relationship to other microsporidia 总被引:1,自引:0,他引:1
Microsporidia are intracellular parasites that are common in invertebrates. Taxonomic classification is mostly restricted
to morphologic and physiologic data. Limited data are available about taxonomic classification using DNA-sequence data for
analysis. We examined the small-subunit (SSU) rDNA, the intergenic spacer (ITS) region, and a part of the large-subunit (LSU)
rDNA of Nosema algerae, a parasite of mosquitoes, taken from a laboratory colony of Anopheles stephensi. Target gene amplifications were done by polymerase chain reaction (PCR) and, after cloning, DNA fragments were sequenced.
The SSU-rDNA sequence obtained was aligned with several other microsporidian SSU-rDNA sequences available from the GenBank
or EMBL data bases and was analyzed by different methods. On the basis of the results of our phylogenetic analysis, we suggest
that our N. algerae isolate is not closely related to other microsporidia belonging to the genus Nosema.
Received: 31 May 1999 / Accepted: 27 July 1999 相似文献
65.
Manfred Rtzsch Stefan Zschoche Volker Steinert Klaus Schlothauer 《Macromolecular chemistry and physics.》1986,187(7):1669-1679
Structural investigations on maleic anhydride (MAn) copolymers with ethene, propene and styrene, their products of hydrolysis, and their methyl half-esters by means of 13C NMR spectroscopy are presented. The spectra of 2,3-diethylsuccinic acid and its anhydrides in the erythro- and threo-configuration and of butylsuccinic acid and its anhydride were obtained and compared with the spectra of the copolymers. In each case the results show the formation of both threo(trans)- and erythro(cis)-structures. At a polymerization temperature of 60°C the proportions were 88% threo to 12% erythro for ethene/MAn copolymers and 80% threo to 20% erythro for propene/MAn copolymers, a ratio which was confirmed also by the hydrolyzed forms. Copolymerization at 150°C leads, in the case of propene/MAn, to 67% threo and 33% erythro. The production of ethene/MA copolymer via the copolymerization of ethene and fumaric acid half-ester and its saponification to ethene/fumaric acid leads to a ratio of 38% threo to 62% erythro. These results are in accordance with the thermal stabilities of the configurations. In the case of styrene/MAn copolymer it is not possible to obtain a unique interpretation of the configurations from the spectra. For the conversion of propene/MAn and styrene/MAn copolymers by means of methanol to half-esters it can be derived from the 13C NMR spectra how many of the half-ester moieties are obtained in the neighbourhood of the methyl and phenyl groups, respectively, of the olefin. 相似文献
66.
Masahiro Oike Gero Schwarz Jan Sehrer Matthias Jost Volker Gerke Klaus Weber Guy Droogmans Bernd Nilius 《Pflügers Archiv : European journal of physiology》1994,428(5-6):569-576
Possible interactions of cytoskeletal elements with mechanically induced membrane currents and Ca2+ signals were studied in human endothelial cells by using a combined patch-clamp and Fura II technique. For mechanical stimulation, cells were exposed to hypotonic solution (HTS). The concomitant cell swelling activates a Cl– current, releases Ca2+ from intracellular stores and activates Ca2+ influx. To interfere with the cytoskeleton, cells were loaded either with the F-actin-stabilizing agent phalloidin (10 mol/l), or the F-actin-depolymerizing substance cytochalasin B (50 mol/l). These were administered either in the bath or the pipette solutions. The tubulin structure of the endothelial cells was modulated by taxol (50 mol/l), which supports polymerization of tubulin, or by the depolymerizing agent colcemid (10 mol/l) both applied to the bath. Immunofluorescence experiments show that under the chosen experimental conditions the cytoskeletal modifiers employed disintegrate the F-actin and microtubuli cytoskeleton. Neither of these cytoskeletal modifiers influenced the HTS-induced Cl– current. Ca2+ release was not affected by cytochalasin B, taxol or colcemid, but was suppressed if the cells were loaded with phalloidin. Depletion of intracellular Ca2+ stores by thapsigargin renders the intracellular [Ca2+] sensitive to the extracellular [Ca2+], which is indicative of a Ca2+ entry pathway activated by store depletion. Neither cytochalasin B nor phalloidin affected this Ca2+ entry. We conclude that F-actin turnover or depolymerization is necessary for Ca2+ release by mechanical activation. The tubulin network is not involved. The Ca2+ release-activated Ca2+ entry is not modulated by the F-actin cytoskeleton. 相似文献
67.
Holt PG Sly PD Martinez FD Weiss ST Björkstén B von Mutius E Wahn U 《Nature immunology》2004,5(7):695-698
The spiraling costs of asthma treatment seem set to continue rising, given the equivocal performance of the latest generation of specific anti-inflammatory drugs in trials in adult asthmatics. We argue that the continuation of this trend is inevitable unless there is a substantial realignment of entrenched drug development policy in the pharmaceutical industry and a parallel shift in licensing policy by regulatory authorities to encourage the development of drugs capable of halting the progression from acute to chronic asthma when the disease first manifests in childhood. The theoretical framework for such an approach, including proof-of-principle data from studies in children with early-stage disease and a range of candidate drugs, already exists. What is needed is informed debate on the risks versus potential benefits of this approach. 相似文献
68.
Klussmann JP Weissenborn SJ Wieland U Dries V Eckel HE Pfister HJ Fuchs PG 《Medical microbiology and immunology》2003,192(3):129-132
Human papillomavirus (HPV) infections are thought to be one of the causal factors in the development of head and neck squamous cell carcinomas (HNSCC), particularly in tumors arising from the Waldeyer's tonsillar ring. We screened 98 carefully stratified HNSCC and different control tissues for the presence of HPV DNA by nested polymerase chain reaction (PCR) specific for genital- and Epidermodysplasia verruciformis (EV)-associated HPVs and by HPV16-specific single step PCR. Typing was performed by direct sequencing and/or sequencing of cloned amplimers. On average HNSCC showed rather low HPV DNA prevalences; 18% of the oral cavity cancers, 8% of nasopharyngeal cancers, 25% of hypopharyngeal cancers and 7% of laryngeal cancers were HPV DNA positive. In contrast, HPV sequences could be detected in 45% of the oropharyngeal cancers, particularly tonsillar carcinomas (58%). Tonsillar carcinomas were significantly more likely to be HPV positive than tumors from any other site ( P<0.001). All tonsillar cancers contained oncogenic HPV types, predominantly HPV16 (13 of 14; 93%). Unaffected tonsils were available from two of these patients, but both tested negative for HPV DNA. Furthermore, no HPV DNA could be found in tonsillar biopsy specimens from control groups. Localization and load of HPV DNA was determined in HPV16-positive tonsillar carcinomas, their metastases and in unaffected mucosa using laser-assisted microdissection and subsequent real time fluorescence PCR. We demonstrated that the HPV genome is located in the cancer cells, whereas the infection of normal mucosa is a rare event. Quantification of HPV16 DNA in samples of seven patients yielded viral loads from 6 to 153 HPV DNA copies per beta-globin gene copy and the load values in both locations were roughly comparable. These loads are comparable with data shown for other HPV-associated lesions. Statistical evaluation of data related to clinicopathological parameters showed a significant correlation of the HPV positivity of tonsillar carcinomas with tumor grading ( P=0.008) and alcohol consumption ( P=0.029). Taken together our findings show a preferential association of HPV DNA with tonsillar carcinomas. Furthermore our results argue for HPV-positive tonsillar carcinomas representing a separate tumor entity, which is less dependent on conventional HNSCC risk factors. 相似文献
69.
Properties of mouse leukemia viruses. XI. Immunoelectron microscopic studies on viral structural antigens on the cell surface. 总被引:14,自引:0,他引:14
Immunoelectron microscopic studies confirmed most of the results of the cytotoxic tests reported by Hunsmann et al. (Hunsmann, et al. (1976). Virology69, 157–168). GP71 and P12 viral structural antigens could be demonstrated on the surface of murine C-virus-producing but not on nonproducing transformed K Balb, MSV85 and HT-1 cells. GP71 serum revealed a type- and group-specific reactivity but failed to demonstrate an interspecies antigenic determinant, probably because of its relatively low corresponding titer. P12 antiserum reacted mainly type specifically. By this method, P10, P15, and P31 antigens were not detectable in significant amounts with the possible exception of P31 antigen on the highly producing FLV-Eveline cell. GP71 antigen occurred on the viral surface as well as on nonbudding areas of the cell membrane. P12 antigen was absent on virus particles but relatively abundant on nonbudding areas of the cell surface. No difference in the distribution of type- and group-specific determinants of GP71 was recognizable, and no clusters of the antigens studied were observed on the membrane under the conditions used. Based on these results it is suggested that among the virus structural antigens only GP71 and P12 antigens are integral surface constituents of the cells investigated and that none of the antigenic determinants studied represents a murine C-virus-induced tumor-specific cell surface antigen (TSSA). The relation of viral structural antigens to cell surface and soluble antigens described earlier and the significance of the results for possible preparation of vaccines are discussed. 相似文献
70.
Properties of mouse leukemia viruses. VIII. The major viral glycoprotein of Friend leukemia virus. Seroimmunological, interfering and hemagglutinating capacities 总被引:30,自引:0,他引:30
Gerhard Hunsmann Volker Moennig Liselotte Pister Eveline Seifert Werner Schäfer 《Virology》1974,62(2):307-318
The purified major glycoprotein (GP71) of Friend leukemia virus revealed type-specific as well as species-specific and interspecies antigenicities in various types of seroimmunological tests. It was also able to induce the production of neutralizing antibodies, to interfere with murine leukemia viruses from two different serotypes, and to hemagglutinate. Demonstration of hemagglutination became possible after reconstitution of GP71 to multivalent complexes by suitable species-specific antibody (indirect hemagglutination). 相似文献