全文获取类型
收费全文 | 79192篇 |
免费 | 6443篇 |
国内免费 | 3074篇 |
专业分类
耳鼻咽喉 | 561篇 |
儿科学 | 1293篇 |
妇产科学 | 1022篇 |
基础医学 | 13758篇 |
口腔科学 | 1164篇 |
临床医学 | 4297篇 |
内科学 | 10091篇 |
皮肤病学 | 1618篇 |
神经病学 | 6441篇 |
特种医学 | 1183篇 |
外国民族医学 | 19篇 |
外科学 | 6475篇 |
综合类 | 9186篇 |
现状与发展 | 8篇 |
预防医学 | 3215篇 |
眼科学 | 877篇 |
药学 | 13048篇 |
8篇 | |
中国医学 | 2394篇 |
肿瘤学 | 12051篇 |
出版年
2024年 | 185篇 |
2023年 | 1406篇 |
2022年 | 2869篇 |
2021年 | 3144篇 |
2020年 | 2554篇 |
2019年 | 2880篇 |
2018年 | 2618篇 |
2017年 | 2569篇 |
2016年 | 2296篇 |
2015年 | 2954篇 |
2014年 | 4141篇 |
2013年 | 4539篇 |
2012年 | 3707篇 |
2011年 | 4547篇 |
2010年 | 3916篇 |
2009年 | 3836篇 |
2008年 | 3890篇 |
2007年 | 3765篇 |
2006年 | 3416篇 |
2005年 | 3060篇 |
2004年 | 2927篇 |
2003年 | 2690篇 |
2002年 | 2156篇 |
2001年 | 1827篇 |
2000年 | 1784篇 |
1999年 | 1472篇 |
1998年 | 1396篇 |
1997年 | 1235篇 |
1996年 | 1049篇 |
1995年 | 904篇 |
1994年 | 693篇 |
1993年 | 614篇 |
1992年 | 565篇 |
1991年 | 481篇 |
1990年 | 392篇 |
1989年 | 373篇 |
1988年 | 337篇 |
1987年 | 315篇 |
1986年 | 318篇 |
1985年 | 625篇 |
1984年 | 721篇 |
1983年 | 462篇 |
1982年 | 537篇 |
1981年 | 478篇 |
1980年 | 417篇 |
1979年 | 371篇 |
1978年 | 320篇 |
1977年 | 231篇 |
1976年 | 203篇 |
1975年 | 159篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
41.
The use of endogenous Protoporphyrin IX generated through the heme biosynthetic pathway after administration of 5-aminolevulinic acid (ALA) has led to many applications in photodynamic therapy (PDT). In Buenos Aires, Argentina, the Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), reported for the first time, in 1975, porphyrin synthesis from ALA in highly dividing plant tissues. Increased porphyrin synthesis in tumours as well as cell photosensitisation was reported soon after. Our group is also interested in studying the use of new synthetic lipophilic derivatives of ALA as well as ALA delivery in liposomes. We have elucidated the mechanism of ALA transport in mammalian and yeast cells. The interactions between ALA-PDT and nitric oxide were investigated in three murine adenocarcinoma cell lines. In the National University of Río Cuarto, Córdoba, a group is devoted to the synthesis of new porphyrin-derived photosensitisers to study their effects on photoinactivation of bacterial and mammalian cells death by PDT. At the Centre of Electron Microscopy of the Cordoba National University, a prototype of a 630 nm noncoherent light source was designed and constructed. Cost of the light source and scarce knowledge of the benefits of PDT by physicians limit the spread of the treatment throughout the country. 相似文献
42.
Joachim Fensterle 《Journal der Deutschen Dermatologischen Gesellschaft》2006,4(3):205-216
Many cellular signaling pathways are involved in the development of cancer. Depending on the tumor entity, the nature as well as the mode of activation can differ. Some signaling pathways frequently show changes as all tumor cells have to fulfill some basic requirements such as independence from growth factors or insensitivity against apoptosis. In this review, the possibilities of a tumor to manipulate signaling pathways to reach these goals are exemplified based on an archetypical melanoma cell. In addition, new therapeutic options based on the knowledge of signaling pathways will be discussed. 相似文献
43.
鸡抗内毒素卵黄抗体IgY的制备 总被引:2,自引:1,他引:1
目的:研究分别应用内毒素(LPS)、类脂A(LipidA)和大肠杆菌突变株15免疫鸡后其蛋黄中抗内毒素抗体IgY的产量、纯度、效价并筛选最佳免疫抗原。方法:分别应用内毒素(LPS)、类脂A(LipidA)和大肠杆菌J5突变株作为抗原免疫25周龄Leghom鸡,水溶法(WD)提取蛋黄中抗体IgY,双紫外光测定抗体含量,SDS-PSGE电泳检测抗体纯度,细胞酶联染色和ELISA检测抗体特异性、效价及筛选最佳免疫抗原。结果:3种抗内毒素IgY含量和效价分别为14.4mg/ml和1:12 800(J5)、10.61mg/ml和1:12 800(LPS)、9.26mg/ml和1:3200(LipidA),抗体纯度均为95%左右。结论:大肠杆菌突变株J5和内毒素(LPS)为最佳免疫抗原,免疫鸡后其蛋黄中抗内毒素抗体IgY的产量和效价最高。 相似文献
44.
J. Kralovanszky N. Prajda S. Kerpel-Fronius T. Bagrij E. Kiss G. J. Peters 《Cancer chemotherapy and pharmacology》1993,32(3):243-248
Selective protection of the normal host tissues from the toxic effects of anticancer agents would allow the use of higher, probably more effective, doses of the drugs. It has been demonstrated that delayed high-dose uridine administration after 5-fluorouracil decreases the extent of myelosuppression and causes faster regeneration of the bone marrow. We studied the biochemical consequences of the gastrointestinal toxicity caused by 5-fluorouracil and the potential of high-dose uridine treatment to influence these adverse effects. 5-Fluorouracil caused dose-related decreases in the biochemical parameters (thymidine kinase, sucrase, maltase, alkaline phosphatase) selected as early markers of the impaired metabolic activity of the intestinal mucosa. The nadir of the biochemical changes was reached between 24 h and 72 h after 5-fluorouracil treatment, and complete regeneration of the mucosa took 6–7 days. Delayed high-dose uridine administration failed to mitigate the severity of the gastrointestinal damage that ensued after 5-fluorouracil treatment, but caused significantly earlier regeneration of the mucosa. 相似文献
45.
B. A. Johnson Donald R. Jasinski Gantt P. Galloway Henry Kranzler Robert Weinreib Raymond F. Anton Barbara J. Mason Michael J. Bohn Helen M. Pettinati Richard Rawson Christopher Clyde 《Psychopharmacology》1996,128(2):206-215
Four hundred and twenty-three alcohol dependent subjects were enrolled into a 12-week randomized, double-blind, placebo-controlled
study to determine the safety and efficacy of the 5-HT2 receptor antagonist, ritanserin (2.5 mg/day or 5 mg/day), in reducing alcohol intake and craving. All subjects received 1
week of single-blind placebo prior to randomization into the 11-week double-blind phase. Additionally, all subjects received
weekly individual sessions of manual-guided cognitive-behavioral therapy. Comparing the single-blind period with endpoint,
there was approximately a 23% reduction in drinks/day; 34% fall in the total number of drinking days/week; 22% decrease in
drinks/drinking day; and a 37% diminution in alcohol craving for all treatment groups. All treatment groups experienced a
beneficial clinical outcome as assessed by the Clinical Global Impression Scale. There was, however, no significant difference
between treatment groups on any of these measures of alcohol drinking, craving, or clinical outcome. Subjects were of relatively
high social functioning at baseline, and this did not change significantly during treatment. Treatment groups did not differ
significantly on either medication compliance or reported adverse events. Ritanserin treatment was associated with a dose-related
prolongation of subjects’ QTc interval recording on the electrocardiogram. These results suggest that alcohol dependent subjects
can show marked clinical improvement within a structured alcohol treatment program. These findings do not support an important
role for ritanserin in the treatment of alcohol dependence.
Received: 30 April 1996/Final version: 3 July 1996 相似文献
46.
目的探讨p16基因突变在白血病发生中的作用及基因突变的机制。方法利用点突变检测仪、水平和垂直板电泳对p16基因的外显子1、外显子2的PCR扩增产物作缺失和点突变分析。结果在白血病35例临床标本中有22例发生缺失突变,6例发生点突变,突变率约80%。在22例缺失突变病例中,有10例为不完全缺失突变即有低于外显子509bp的扩增产物。结论p16基因含有“GC”DNA重复顺序,易发生DNA重组及易位和重排。在白血病发生中起重要作用 相似文献
47.
Serotonin (5-HT) is a mediator (through 5-HT1P receptors) of slow EPSPs in myenteric ganglia of the small intestine. The effect of 5-HT can be mimicked by elevating cAMP; therefore, we tested the hypothesis that the slow EPSP-like response to 5-HT is cAMP-mediated. Guinea pig gut was enzymatically dissociated; myenteric ganglia remained intact and were collected by filtration. Neurons in the isolated ganglia retained their ability to manifest the slow EPSP-like response to 5-HT. Exposure to 5-HT raised the ganglionic level of cAMP (ED50 0.3 μM). This effect was not antagonized by the 5-HT1P antagonist, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (100.0 μM), or mimicked by the 5-HT1P agonist, 5-hydroxyindalpine (10.0 μM). Increases in cAMP were also evoked by the 5-HT1 agonist, 5-carboxyamidotryptamine (10.0 μM), the 5-HT2 agonist, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 1.0–10.0 μM), and by the 5-HT4 agonists, renzapride (1.0–10.0 μM) and 5-methoxytryptamine (1.0–10.0 μM); however, neither the 5-HT1/5-HT2 antagonists, spiperone, methysergide, and methiothepin, nor the 5-HT4 antagonist, tropisetron (ICS 205–930; 10.0 μM), were able to inhibit the rise in cAMP evoked by these compounds or by 5-HT (0.1–10.0 μM). The 5-HT-evoked elevation of cAMP was antagonized by ketanserin (10.0 μM), which also blocked the effects of 5-methoxytryptamine and DOI, but not those of renzapride. The effective concentration of DOI, however, was higher than that needed for activation of 5-HT2 receptors, and Northern analysis using a cDNA probe encoding the rat 5-HT2 receptor failed to reveal the presence of 5-HT2 mRNA in myenteric ganglia, although it hybridizes with mRNA of the right size in the guinea pig brain. Compounds that failed to change levels of cAMP or to antagonize the action of 5-HT included 8-hydroxy-di-n-propylamino tetralin, R58639, R88226, and sumatriptan. It is concluded that the receptor responsible for the 5-HT-induced rise in cAMP in ganglia isolated from the guinea pig myenteric plexus is not a known subtype of 5-HT receptor. Since the pharmacology of this novel receptor is different from that of the slow EPSP-like response to 5-HT, the receptor probably does not mediate the slow EPSP. © 1993 Wiley-Liss, Inc. 相似文献
48.
What is the value of bcl-2 protein detection for histopathologists? 总被引:15,自引:0,他引:15
49.
BACKGROUND: The responses of mice to the mite allergen Der p 1 have been used to study the mechanisms of allergic sensitization and the development of new types of immunotherapy. Many of the studies require a knowledge of the T cell epitopes, and because Der p 1 is polymorphic, the effect of natural amino acid substitution in the allergen. The intranasal administration of peptides containing T cell epitopes can induce a mucosal tolerance but it is not known if the major activity is limited to stimulatory peptides and if, as found for autoimmunity, some epitopes are not inhibitory. OBJECTIVE: To determine and compare the sequences of Der p 1 which contain stimulatory epitopes for the high responding H-2(b) and H-2(q) mice and the sequences which induce tolerance by intranasal administration of peptides. METHODS: T cell responses of mice immunized with Der p 1 were measured by in vitro T cell stimulation assays so an extensive study of epitope recognition and intranasal tolerance could be made. Synthetic peptides were used to examine the stimulatory and inhibitory ability of all Der p 1 sequences and to map the major H-2(b) epitope in detail. This included the effect of the common polymorphic amino acid 124 substitution found within this epitope. RESULTS: Three and two regions, respectively, were found to contain stimulatory T cell epitopes for H-2(b) and H-2(q) mice. The peptides in these regions were also the most active at inducing intranasal tolerance for the responding haplotype. The correspondence between inhibitory and stimulatory peptides was maintained for the fine mapping of the major H-2(b) epitope. This was found about a core region of 118-126 which was overlapping but separate to a consensus sequence for the binding of endogeneous peptides. Peptides with alanine at the naturally polymorphic residue 124 stimulated and inhibited responses to Der p 1 more effectively, while peptides with the valine 124 variant were immunogenic but poorly cross-reactive. CONCLUSIONS: The intranasal administration of peptides representing each of five epitopes recognized by two strains of mice were able to induce mucosal tolerance and the major tolerizing activity was limited to these epitopes. The position of the core major epitope for C57 mice, which differs from a previously predicted epitope, and its specificity for the natural alanine 124 variant is described. 相似文献
50.
The present study examined the influences of dopamine (DA) receptor stimulation on enkephalin (Met5-enkephalin; ME) and tachykinin (substance P; SP) systems of basal ganglia of Sprague-Dawley rats, lesioned as neonates with 6-hydroxydopamine (6-OHDA). It has been proposed that the neonatal 6-OHDA-lesioned rat could serve as a model for the DA deficiency and self-injurious behavior (SIB) observed in the childhood neurological disorder. Lesch-Nyhan syndrome. In agreement with earlier work, the present study found that the neonatal 6-OHDA treatment at 3 days of age, reduced DA and caused an increase in ME and a decrease in SP content in the striatum and substantia nigra, when tested as adults. Administration of the DA precursor, L-dihydroxyphenylalanine (L-DOPA), to lesioned animals, induced SIB; increased DA and DOPAC levels; produced a greater decrease (-64%) in SP levels in the striatum and substantia nigra than was observed with lesion alone (-28%). The L-DOPA-induced decrease in SP levels and the SIB observed in the lesioned animals were blocked by pretreatment with the D1 receptor antagonist, SCH-23390. Moreover, administration of the D1 receptor agonist, SKF-38393, but not the D2 agonist, LY-171555, to lesioned animals mimicked the L-DOPA responses in all respects, except that the agonists did not alter DA or DOPAC levels. None of the DA agonists or antagonists treatments affected lesion-induced increase in ME levels in the striatum. These results indicate for the first time, that SIB precipitated by DA agonists in neonatal dopaminergic denervated animals, is associated with a marked and selective decrease in SP in the striatonigral SP neurons. This process has two components: (a) a retarded development of the SP system due to neonatal dopaminergic denervation: and (b) a depletion of the remaining SP, presumably by enhanced release due to D1 DA receptor-mediated activation of striatonigral SP neurons. 相似文献