全文获取类型
收费全文 | 12189篇 |
免费 | 958篇 |
国内免费 | 361篇 |
专业分类
耳鼻咽喉 | 82篇 |
儿科学 | 230篇 |
妇产科学 | 137篇 |
基础医学 | 2758篇 |
口腔科学 | 94篇 |
临床医学 | 721篇 |
内科学 | 1927篇 |
皮肤病学 | 150篇 |
神经病学 | 505篇 |
特种医学 | 183篇 |
外科学 | 890篇 |
综合类 | 1567篇 |
预防医学 | 1252篇 |
眼科学 | 75篇 |
药学 | 1193篇 |
7篇 | |
中国医学 | 621篇 |
肿瘤学 | 1116篇 |
出版年
2024年 | 42篇 |
2023年 | 290篇 |
2022年 | 556篇 |
2021年 | 720篇 |
2020年 | 665篇 |
2019年 | 440篇 |
2018年 | 370篇 |
2017年 | 517篇 |
2016年 | 485篇 |
2015年 | 562篇 |
2014年 | 791篇 |
2013年 | 703篇 |
2012年 | 663篇 |
2011年 | 833篇 |
2010年 | 514篇 |
2009年 | 453篇 |
2008年 | 482篇 |
2007年 | 508篇 |
2006年 | 463篇 |
2005年 | 359篇 |
2004年 | 298篇 |
2003年 | 322篇 |
2002年 | 234篇 |
2001年 | 205篇 |
2000年 | 179篇 |
1999年 | 174篇 |
1998年 | 130篇 |
1997年 | 129篇 |
1996年 | 135篇 |
1995年 | 113篇 |
1994年 | 126篇 |
1993年 | 93篇 |
1992年 | 89篇 |
1991年 | 78篇 |
1990年 | 75篇 |
1989年 | 77篇 |
1988年 | 82篇 |
1987年 | 48篇 |
1986年 | 60篇 |
1985年 | 66篇 |
1984年 | 88篇 |
1983年 | 50篇 |
1982年 | 69篇 |
1981年 | 47篇 |
1980年 | 39篇 |
1979年 | 26篇 |
1978年 | 14篇 |
1977年 | 15篇 |
1976年 | 13篇 |
1975年 | 6篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
101.
Strong cellular and humoral anti-HIV Env immune responses induced by a heterologous rhabdoviral prime-boost approach 总被引:4,自引:0,他引:4
Recombinant rhabdovirus vectors expressing human immunodeficiency virus (HIV) and/or simian immunodeficiency virus (SIV) proteins have been shown to induce strong immune responses in mice and rhesus macaques. However, the finding that such responses protect rhesus macaques from AIDS-like disease but not from infection indicates that further improvements for these vectors are needed. Here, we designed a prime-boost schedule consisting of a rabies virus (RV) vaccine strain and a recombinant vesicular stomatitis virus (VSV) both expressing HIV Envelope (Env). Mice were primed and boosted with the two vaccine vehicles by different routes and in different combinations. Mucosal and systemic humoral responses were assessed using enzyme linked immunosorbent assay (ELISA) while the cellular immune response was determined by an IFN-gamma ELISPOT assay. We found that an immunization combination of RV and VSV elicited the highest titers of anti-Env antibodies and the greatest amount of Env-specific IFN-gamma secreting cells pre- and post-challenge with a recombinant vaccinia virus expressing HIV(89.6) Env. Furthermore, intramuscular immunization did not induce antigen-specific mucosal antibodies while intranasal inoculation stimulated vector-specific IgA antibodies in vaginal washings and serum. Our results show that it is feasible to elicit robust cellular and humoral anti-HIV responses using two different live attenuated Rhabdovirus vectors to sequentially prime and boost. 相似文献
102.
At older ages, the circadian rhythm of body temperature shows a decreased amplitude, an advanced phase, and decreased stability. The present review evaluates to what extent these changes may result from age-related deficiencies at several levels of the thermoregulatory system, including thermoreception, thermogenesis and conservation, heat loss, and central regulation. Whereas some changes are related to the aging process per se, others appear to be secondary to other factors, for which the risk increases with aging, notably a decreased level of fitness and physical activity. Moreover, functional implications of the body temperature rhythm are discussed. For example, the relation between circadian rhythm and thermoregulation has hardly been investigated, while evidence showed that sleep quality is dependent on both aspects. It is proposed that the circadian rhythm in temperature in homeotherms should not be regarded as a leftover of ectothermy in early evolution, but appears to be of functional significance for physiology from the level of molecules to cognition. A new view on the functional significance of the circadian rhythm in peripheral vasodilation and the consequent out-of-phase rhythms in skin and core temperature is presented. It is unlikely that the strong, daily occurring, peripheral vasodilation primarily represents heat loss in response to a lowering of set point, since behavioral measures are simultaneously taken in order to prevent heat loss. Several indications rather point towards a supportive role in immunological host defense mechanisms. Given the functional significance of the temperature rhythm, research should focus on the feasibility and effectiveness of methods that can in principle be applied in order to enhance the weakened circadian temperature rhythm in the elderly. 相似文献
103.
壳聚糖纳米颗粒包裹对鼠白细胞介素2基因表达和调节小鼠免疫效应的影响 总被引:4,自引:0,他引:4
本实验制备壳聚糖纳米颗粒 (CNP) ,包裹小鼠白细胞介素 2基因 (mIL 2 )真核表达质粒 (VRMIL 2 ) ,肌注接种 2 1d昆明小鼠 ,观察mIL 2基因体内表达及其对免疫应答和免疫保护的影响。实验结果发现 :CNP包裹VRMIL 2注射小鼠血液中IgG、IgM和IgA不同程度地增多 ,均显著高于CNP包裹空白质粒组 (P <0 .0 5 ) ;其血清中IL 2、IL 4和IL 6的含量明显升高 ,与对照组差异显著 (P <0 .0 5 ) ;外周血液的白细胞和淋巴细胞数量也较对照组显著增加。免疫后 35d以大肠杆菌口服攻毒实验小鼠 ,检测发现 :CNP包裹VRMIL 2组小鼠的上述免疫指标除中性粒细胞外均显著多于对照小鼠 ,VRMIL 2接种小鼠均健康存活 ,而对照小鼠均发病 ;尽管CNP包裹VRMIL 2接种小鼠的体液和细胞免疫指标与未包裹VRMIL 2免疫鼠差异不显著 (P >0 .0 5 ) ,但剂量仅为后者的 1/ 5。这些结果表明 :壳聚糖纳米颗粒包裹VRMIL 2可显著提高外源IL 2基因体内表达水平 ,明显增强体液和细胞免疫水平的效应 ,增强对大肠杆菌的抗病力 ,提示壳聚糖纳米颗粒包裹IL 2基因可明显增强动物的体液和细胞免疫 ,可作为有效的抗感染免疫调节剂。 相似文献
104.
An outbreak of hepatitis A occurred in a rural elementary school in Colbert County, Alabama, in October and November 1972. The outbreak was caused by sewage-contaminated drinking water and involved 49 children and 1 adult. Acute and convalescent serum samples were obtained from the hepatitis patients, and from each of 24 unafflicted matched controls at the same time. Strinkingly, the levels of the third and fourth components of complement (C'3 and C'4) were markedly reduced in the acute samples from the sick children but returned to normal in the convalescent ones; the C'3 and C'4 levels in the healthy matched controls were not reduced. In addition, antigen-antibody complexes were found in convalescent sera from some of the sick children. These findings indicate that immune complexes are present in acture hepatitis A and suggest that the techniques for future virus isolation may have to be altered. 相似文献
105.
目的 研究重组白细胞介素18(rIL-18)对肺炎链球菌肺炎小鼠Th1/ Th2免疫应答的影响.方法 鼻腔接种肺炎链球菌建立小鼠肺炎链球菌肺炎模型,将Balb/c小鼠24只随机分为3组,分别为对照组,肺炎组和肺炎rIL-18干预组(n=8 ),RT-PCR法检测各组小鼠肺组织中IFN-γ、IL-4 mRNA 的表达,同时支气管肺泡灌洗液(BALB)进行活菌计数,有核细胞分类计数.结果 ①肺炎rIL-18干预组BA LF中性粒细胞和巨噬细胞计数显著高于肺炎组和对照组(P<0.001);②肺炎rIL-18 干预组BALF活菌计数显著低于肺炎组(P<0.001);③肺炎rIL-18干预组肺组织IFN- γ mRNA表达上调而IL-4 mRNA表达下调(P<0.001).结论 在小鼠肺炎链球菌肺炎早期给予rIL-18可诱导IFN-γ的合成,促进Th1免疫应答,使Th1/ Th2免疫平衡向Th1免疫偏移、促进宿主对肺炎链球菌的防御. 相似文献
106.
Treponema pallidum subsp. pallidum is the causative a gents of syphilis. Presently, the annual infection rate ofdomestic and international syphilis remains rather high [1,2]. Apart from the serious nature of the disease itself, anumber of studies sugg… 相似文献
107.
Franco Dallegri Franco Patrone Guido Frumento Alberto Ballestrero Carlo Sacchetti 《Journal of clinical immunology》1984,4(6):439-444
Normal human neutrophils were found to destroy ox red blood-cell targets when incubated on micropore filters coated with aggregated IgG, as determined by the51Cr release method. An intact neutrophil oxidative metabolism was essential for the cytotoxic event, since cells from patients with chronic granulomatous disease failed to exert any cytolysis. The target-cell destruction was prevented by catalase, azide, and cyanide and was enhanced by superoxide dismutase, suggesting involvement of the myeloperoxidase-hydrogen peroxide system. Neutrophil-mediated cytotoxicity was markedly amplified by the chemotactic peptideN-formyl-methionyl-leucylphenylalanine, as a result of an increased activity of the myeloperoxidase-hydrogen peroxide cytolytic system itself. This system of cytotoxicity provides a direct evidence for the neutrophil capacity of destroying bystander target cells under conditions simulating thein vivo immunologically mediated tissue injury and offers an excellent model to study events occurring during immune complex diseases.Supported by Grant 83.00902.96/115.11547 from the Italian CNR-PFCCN. 相似文献
108.
Luis C. Antn Sol Ruiz Elena Barrio Guillermo Marqus Angel Snchez Fernando Vivanco 《European journal of immunology》1994,24(3):599-604
The covalent binding reaction of the third component of complement (C3) with rabbit IgG immune aggregates has been studied by enzymic digestion of C3b-IgG adducts. In these adducts C3b was radioactively labeled in the free thiol group generated during activation of the internal thioester of C3. Trypsin digestion of 14C-labeled C3b-IgG adducts degrades C3b to a small antibody-bound 14C-labeled C3 fragment (14C-C3frg), whereas the antibody remains unaltered. Papain digestion of trypsin-treated 14C-C3frg-IgG complexes generated Fc and Fab fragments bearing equivalent amounts of covalently bound 14C-C3frg (43% and 40%, of the total C3 present in the aggregates, respectively). Hydroxylamine treatment of the 14C-C3frg-Fab and 14C-C3frg-Fc complexes released a 14C-C3frg of similar size (about 3–4 kDa) in which the N-terminal residue was the radiolabeled Cys1010. A fragment with the same radioactive N terminus and characteristics was obtained by sequential trypsin and papain digestion of purified C3 labeled with iodo–[14C] acetamide. Affinity-purified 14C-C3frg-Fc complexes digested with pepsin generated a mixture of radioactive peptides, most probably complexes formed by 14C-C3frg and Cγ2 or the hinge digestion products, and 14C-C3frg-pFc' complexes. The latter was also immunoprecipitated with anti-Fc-Sepharose from the pepsin digestion supernatants of 14C-labeled-C3b-IgG complexes. Taken together these data indicate that, during complement activation through the alternative pathway by IgG immune aggregates, C3 is not bound to a single site on the antibody molecule. Both Fab and Fc regions of IgG are equally efficient targets for C3 anchorage. In addition, the data confirm the pFc' as a region of C3 attachment within the Fc portion, and strongly suggest that C3b is bound either to the Cγ2 domain or the hinge or both. 相似文献
109.
The development of the antibody repertoire in newborn mice is greatly influenced by idiotypic network interactions. It has been demonstrated that anti-idiotypic antibodies either directly injected or transferred from the mother may alter the repertoire for life. For an elucidation of the underlying mechanisms we have analyzed the primary immune response to 2-phenyl-5-oxazolone (phOx) coupled to chicken serum albumin (CSA) in BALB/c mice after complete disappearance of maternal antibodies which originated from different stages of affinity maturation. Depending on the serum titers of the mothers after primary (1° mo), secondary (2° mo) or tertiary (3° mo) immunization, maternal anti-phOx IgG persisted in F1 mice for up to 9 months. In addition, F1 mice born to 2° mo developed – even without immunization – an anti-phOx IgM titer which reached levels similar to an antigen-induced primary response. An enhancement of the early primary anti-phOx as well as anti-CSA response was seen in F1 mice born from 1° mo, whereas the response was delayed when born to 2° mo and 3° mo. The antibody titers in the latter group of mice remained at a lower level for 3 months. In contrast, mice of the F2 generation which received a smaller amount of the same collection of maternal antibodies as F1 mice from 3° mo exhibited a quite different primary response: (i) They showed an earlier onset in their anti-CSA response. (ii) Whereas normally a plateau in antibody titer was reached by the 4th weak after immunization, in 55 % of the F2 mice a prolonged increase of the anti-phOx and anti-CSA antibody titers was observed. At 12 weeks after antigenic challenge, titers reached plateau levels of 6 × 105 which were never before seen in a primary phOx or CSA response. Thus, depending on its own immunological experience, the maternal immune system induces a state of memory in the offspring which results in a faster and/or enhanced immune response in the F1 and F3 generations. 相似文献
110.
目的探讨静脉应用T-bet重组腺病毒(AdT-bet)对哮喘模型小鼠过敏性气道炎症及Th1/Th2免疫失衡的影响。方法36只C57BL/6小鼠随机分为AdT-bet治疗组(A组)、模型对照组(B组)、正常组(C组)。以卵蛋白(OVA)、氢氧化铝免疫建立哮喘模型,A组激发前尾静脉注射100μL的AdT-bet(1×10^8 PFU/μL),各组激发后肺泡灌洗分析细胞组份,分离肺淋巴细胞测定细胞因子分泌水平,以流式细胞仪检测CD3^+、CD4^+ T细胞比例及表达IFNγ和IL-4的比例,比较各组肺组织学改变。结果静脉应用AdT-bet组与对照组相比:①可明显抑制抗原激发后气道内嗜酸性粒细胞的浸润(P〈0.01);②明显抑制肺淋巴细胞产生IL-4、IL-5,增加了IFNγ的产生;③肺脏淋巴细胞CD4^+ IFNγ百分比及IFNγ^+/IL-4^+明显升高(P〈0.01),而CD4^+ IL-4^+百分比则明显下降;④明显抑制哮喘鼠气道内及肺泡内的过敏性炎症反应。结论激发前静脉用AdT-bet对哮喘小鼠过敏性气道炎症有明显的防治作用,其机制可能与表达的T-bet上调Th1/Th2比值,从而调整了免疫平衡有关。 相似文献