全文获取类型
收费全文 | 152031篇 |
免费 | 11525篇 |
国内免费 | 6262篇 |
专业分类
耳鼻咽喉 | 766篇 |
儿科学 | 3032篇 |
妇产科学 | 1711篇 |
基础医学 | 23452篇 |
口腔科学 | 2552篇 |
临床医学 | 12045篇 |
内科学 | 25379篇 |
皮肤病学 | 2365篇 |
神经病学 | 13390篇 |
特种医学 | 2344篇 |
外国民族医学 | 32篇 |
外科学 | 10055篇 |
综合类 | 21388篇 |
现状与发展 | 35篇 |
预防医学 | 9514篇 |
眼科学 | 2085篇 |
药学 | 22432篇 |
21篇 | |
中国医学 | 5792篇 |
肿瘤学 | 11428篇 |
出版年
2024年 | 245篇 |
2023年 | 1813篇 |
2022年 | 3356篇 |
2021年 | 5244篇 |
2020年 | 4480篇 |
2019年 | 4740篇 |
2018年 | 4670篇 |
2017年 | 4656篇 |
2016年 | 4971篇 |
2015年 | 5633篇 |
2014年 | 8975篇 |
2013年 | 10624篇 |
2012年 | 9326篇 |
2011年 | 10649篇 |
2010年 | 8683篇 |
2009年 | 7993篇 |
2008年 | 8044篇 |
2007年 | 7613篇 |
2006年 | 6763篇 |
2005年 | 6151篇 |
2004年 | 5210篇 |
2003年 | 4550篇 |
2002年 | 3590篇 |
2001年 | 3097篇 |
2000年 | 2569篇 |
1999年 | 2323篇 |
1998年 | 2085篇 |
1997年 | 1882篇 |
1996年 | 1579篇 |
1995年 | 1346篇 |
1994年 | 1247篇 |
1993年 | 1077篇 |
1992年 | 931篇 |
1991年 | 874篇 |
1990年 | 754篇 |
1989年 | 613篇 |
1988年 | 585篇 |
1987年 | 486篇 |
1986年 | 457篇 |
1985年 | 1209篇 |
1984年 | 1392篇 |
1983年 | 1046篇 |
1982年 | 1190篇 |
1981年 | 1100篇 |
1980年 | 844篇 |
1979年 | 733篇 |
1978年 | 546篇 |
1977年 | 441篇 |
1976年 | 486篇 |
1975年 | 374篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
161.
ALVARO MARTÍNEZ DEL POZO MARIA GASSET MERCEDES O
ADERRA JOS G. GAVILANES 《Chemical biology & drug design》1989,34(5):416-422
α-Sarcin binds one Zn(II) cation per protein molecule, with a Kd value of 0.9 mM, determined by equilibrium dialysis experiments. Ca(II), Mg(II), and Mn(II) do not bind to α-sarcin. Cd(II) and Co(II) also behave as Zn(II). The binding produces local modifications on the protein conformation affecting the microenvironment of tryptophan residues. The three cations modify the fluorescence emission of the protein. The near-u. v. circular dichroism spectrum of the protein is also altered. The binding of Zn(II) and related cations does not modify the secondary structure of the protein. The ribonucleolytic activity of a-sarcin is inhibited upon Zn(II) binding, but no alteration of the ability of the protein to aggregate phospholipid vesicles has been observed. 相似文献
162.
Francisco Jose Martinez-Guijarro Eduardo Soriano Jose Antonio del Rio Carlos Lopez-Garcia 《Brain research》1991,547(2)
An antibody against the calcium binding protein parvalbumin selectively labels a set of neurons in the cerebral cortex of lizards. Golgi-like immunostained bipolar, multipolar and pyramid-like neurons appear mainly located in the inner plexiform layers. Parvalbumin-immunoreactive (PARV-IR) puncta are concentrated in the cell layer of the dorsal and dorsomedial cortices showing a basket-like distribution. The morphology and distribution of PARV-IR neurons and puncta overlap GABA-immunostaining in the cerebral cortex of lizards. Thus, it is likely that PARV-IR neurons are a subset of the cortical GABAergic neurons of lizards. 相似文献
163.
The role of intracellular Zn2+ in the translocation of protein kinase C from cytosol to membrane fractions was examined by the [3H]phorbol 12,13-dibutyrate (PDBu) binding method in guinea pig cerebral synaptoneurosomes. N-methyl-d-aspartate (NMDA, 100 μM) and calcium ionophore A23187 (0.3–30 μM) decreased the binding activity in the cytosol with a concomitant increase in the membrane fractions. Pretreatment of synaptoneurosomes with a heavy metal chelator, N,N,N′,N′-tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN), inhibited the NMDA- and A23187-induced changes of the distribution of [3H]PDBu binding sites in cytosol and membrane fractions. The inhibitory effect of TPEN was negated by a preincubation of TPEN with equimolar Zn2+ but not by that with Ca2+. The addition of 500 μM Zn2+ to the lysate of synaptoneurosomes induced an increase of [3H]PDBu binding activity in the membrane fraction with a concomitant decrease in the cytosol fraction, as did 100 μM Ca2+. Low concentrations of Zn2+ (10 μM), which alone had no effect on the distribution of the binding, significantly enhanced the effect of 10 μM Ca2+ in the lysate. Under those conditions TPEN inhibited the Zn2+-potentiated Ca2+-dependent changes in the binding. These results suggest that intracellular Zn2+ is essential for the agonist-induced translocation of protein kinase C in guinea pig synaptoneurosomes. 相似文献
164.
目的探讨急性冠脉综合征(ACS)患者血浆瘦素(LP)及C-反应蛋白(CRP)水平的变化及其临床意义。方法测定急性心肌梗死组(AMI组)、不稳定型心绞痛组(UA组)、对照组(健康体检者)血浆LP及CRP浓度,分析LP、CRP与病情严重程度的关系以及LP与CRP的相关性。结果AMI组、UA组患者血浆LP、CRP浓度较对照组显著升高(P<0.01),2组患者血浆LP与CRP浓度之间均呈显著正相关;AMI组血浆LP、CRP浓度比UA组明显升高(P<0.05)。结论血浆LP及CRP浓度与ACS病情严重性呈正相关,且LP与CRP浓度呈正相关。说明LP与CRP共同参与组织炎症反应,是ACS重要的危险因素及预测因子。 相似文献
165.
目的观察高+Gz重复暴露后脑组织星形胶质细胞中胶质纤维酸性蛋白(GFAP)表达的变化。方法SD大鼠30只,随机分为对照组和+10G;暴露组。+G2暴露组的大鼠暴露于+10Gz/45S,共暴露5次,中间间隔5min。分别于+Gz暴露后不同时间灌注取脑,免疫组织化学染色观察脑GFAP的表达情况。结果+Gz暴露后1d、2d,顶叶皮层、海马GFAP阳性细胞数较对照组均显著增多(P〈0.05),以弱阳性细小型为主;暴露后4d、6d,顶叶皮层、海马GFAP阳性细胞数较对照组进一步增多(P〈0.01),以中等阳性细胞为主,肥大的GFAP增多。结论重复暴露+10Gz/45s可引起大鼠顶叶皮层、海马GFAP表达显著增加。 相似文献
166.
167.
Andressa A.F.L. Maciel Reinaldo B. Ori Manuel B. Braga-Neto Andra B. Braga Eunice B. Carvalho Herene B.M. Lucena Gerly A.C. Brito Richard L. Guerrant Aldo A.M. Lima 《Toxicon》2007,50(8):1027-1040
Vitamin A (retinol), a fat-soluble vitamin, is an essential nutrient for the normal functioning of the visual system, epithelial cell integrity and growth, immunity, and reproduction. Our group has investigated the effect of high doses of oral vitamin A on early childhood diarrhea in our prospective community-based studies from Northeast Brazil and found a beneficial role in reducing the mean duration but not incidence of diarrheal episodes. In this study, we explored the role of retinol supplementation in intestinal cell lines following Clostridium difficile toxin A (TxA) challenge. C. difficile is the most common anaerobic pathogen borne with antibiotic-borne diarrhea and pseudomembranous colitis. Since retinol is critical for the integrity of tight junctions and to modulate the cell cycle, we have focused on changes in transepithelial electrical resistance (TEER) in Caco-2, a more differentiated intestinal cell line, and on models of cell proliferation, migration and viability in IEC-6 cells, an undifferentiated crypt cell line, following TxA injury. In this model, retinol therapy reduced apoptosis, improved cell migration and proliferation, and prevented the reduction in TEER, following C. difficile TxA challenge in a glutamine-free medium. These results suggest the role of retinol in protecting intestinal epithelial barrier function from C. difficile TxA enterotoxic damage. 相似文献
168.
169.
Bacterial ghosts (BGs) are empty bacterial envelopes of Gram-negative bacteria produced by controlled expression of cloned gene E, forming a lysis tunnel structure within the envelope of the living bacteria. BGs are devoid of cytoplasmic content and possess all bacterial bio-adhesive surface properties in their original state while not posing any infectious threat. BGs are ideally suited as an advanced drug delivery system (ADDS) for toxic substances in tumor therapy. The inner space of BGs can be loaded with either single components or combinations of peptides, drugs or DNA which provides an opportunity to design new types of (polyvalent) drug delivery vehicles. Uptake of BGs loaded with Doxorubicin (Dox) by CaCo2 cells led to effective Dox release from endo-lysosomal compartments and accumulation in the nucleus. Viability and proliferative capacity of the cells were significantly decreased (2–3 orders of magnitude) after internalization of Dox loaded BGs as compared to cells incubated with free Dox. The same effect was observed with leukemia cells. Melanoma cells also revealed a high capability to internalize BGs. These results indicate that BGs are able to target a range of types of cancer. BGs have also been investigated as DNA delivery vectors. Studies show DNA loaded BGs are efficiently phagocytosed and internalized by both professional APCs and tumor cells with up to 82% of cells expressing the plasmid-encoded reporter gene. Our studies with BGs as an ADDS system contribute (i) to optimize drug delivery for the treatment of cancer; (ii) define specific conditions for selection and preparation of BG formulations; (iii) and provide a background for the clinical application of BGs in cancer therapy. 相似文献
170.
P. Vondracek M. Hermanova J. Sedlackova L. Fajkusova D. Stary A. Michenkova R. Gaillyova P. Seeman R. Mazanec 《European journal of neurology》2007,14(10):1182-1185
We report a 24-year-old male with an unusual combination of two inherited neuromuscular disorders – Charcot-Marie-Tooth (CMT) disease type 1A and Duchenne muscular dystrophy (DMD). A phenotypic presentation of this patient included features of both these disorders. Nerve conduction studies revealed demyelinating peripheral neuropathy. Electromyography showed a profound myogenic pattern. The serum creatine kinase level was highly elevated. Muscle biopsy revealed a dystrophic picture with deficient dystrophin immunostaining. CMT1A duplication on chromosome 17p11.2 was found. The frame-shift mutation c.3609–3612delTAAAinsCTT (p.K1204LfsX11) was detected in the dystrophin gene by analysing mRNA isolated from the muscle tissue. The patient inherited both these mutations from his mother. The combination of CMT1A and DMD has not been reported as yet. 相似文献