全文获取类型
收费全文 | 3008篇 |
免费 | 213篇 |
国内免费 | 3篇 |
专业分类
耳鼻咽喉 | 25篇 |
儿科学 | 76篇 |
妇产科学 | 68篇 |
基础医学 | 380篇 |
口腔科学 | 37篇 |
临床医学 | 372篇 |
内科学 | 532篇 |
皮肤病学 | 33篇 |
神经病学 | 172篇 |
特种医学 | 183篇 |
外国民族医学 | 1篇 |
外科学 | 387篇 |
综合类 | 25篇 |
一般理论 | 1篇 |
预防医学 | 293篇 |
眼科学 | 86篇 |
药学 | 259篇 |
中国医学 | 25篇 |
肿瘤学 | 269篇 |
出版年
2023年 | 40篇 |
2022年 | 124篇 |
2021年 | 194篇 |
2020年 | 108篇 |
2019年 | 100篇 |
2018年 | 104篇 |
2017年 | 87篇 |
2016年 | 76篇 |
2015年 | 98篇 |
2014年 | 130篇 |
2013年 | 162篇 |
2012年 | 226篇 |
2011年 | 198篇 |
2010年 | 120篇 |
2009年 | 111篇 |
2008年 | 140篇 |
2007年 | 149篇 |
2006年 | 163篇 |
2005年 | 131篇 |
2004年 | 116篇 |
2003年 | 111篇 |
2002年 | 89篇 |
2001年 | 54篇 |
2000年 | 48篇 |
1999年 | 64篇 |
1998年 | 21篇 |
1997年 | 22篇 |
1996年 | 16篇 |
1995年 | 12篇 |
1994年 | 10篇 |
1992年 | 28篇 |
1991年 | 16篇 |
1990年 | 15篇 |
1989年 | 17篇 |
1988年 | 16篇 |
1987年 | 14篇 |
1986年 | 17篇 |
1985年 | 5篇 |
1984年 | 9篇 |
1983年 | 11篇 |
1982年 | 6篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1979年 | 7篇 |
1976年 | 5篇 |
1975年 | 3篇 |
1974年 | 6篇 |
1973年 | 3篇 |
1968年 | 2篇 |
1964年 | 2篇 |
排序方式: 共有3224条查询结果,搜索用时 265 毫秒
1.
Modulation of calcium-activated chloride current via pH-induced changes of calcium channel properties in cone photoreceptors. 总被引:9,自引:0,他引:9
The activity of calcium-activated chloride channels is controlled through the complex interaction of cellular mechanisms affecting calcium entry, buffering, and extrusion, and an unknown stoichiometric relation between intracellular Ca concentration and Cl channel activation. Here, we show that calcium-activated chloride current [ICl(Ca)] in cone photoreceptors is also highly sensitive to external pH, being strongly reduced by acidification and enhanced by alkylinization of the bathing medium. We propose that this modulation is accounted for by the pH sensitivity of Ca channel activation and permeation, already well characterized in other cells, which we now extend to cone photoreceptor Ca channels. Acidification of the external medium from a control pH of 7.4 shifts the Ca channel activation range positively by about 10 mV at pH 6.8, reducing the magnitude of calcium current with a consequent reduction of chloride current. Alkylinization shifts the Ca channel activation range negatively by about 8 mV at pH 8 and produces larger calcium currents during step depolarizations that in turn elicit larger chloride tail currents. Modulation of ICl(Ca) by pH suggests other consequences of the pH-induced shift in Ca channel gating, for one, modification of Ca-dependent transmitter release, which could be especially significant in photoreceptors where the cell's operating voltage range overlaps only the lower end of the Ca channel activation range. 相似文献
2.
J C Mason K S Ordelheide G M Grames T V Thrasher R D Harris R H Bui M C Mackett 《Transplantation》1987,44(4):588-591
3.
High-dose methotrexate (MTX) toxicity is reduced by a non-toxic dose of 5-fluorouracil (FU) when these agents are used in combination. Changes in the hematopoietic system (platelets, erythrocytes, leukocytes, hemoglobin, and hematocrit), ileal tissue, body weight, and mean survival were used as parameters to assess toxicity. For all parameters studied, there were no significant differences between the scheduling of MTX (245 mg/kg) after a priming dose of FU (25 mg/kg), simultaneous MTX and FU, FU alone, and control. However, sequential treatment with MTX followed by FU, and MTX alone resulted in: a marked decrease in the hematopoietic parameters; significant morphological changes in ileal tissue; a reduction of body weight; and increased mortality of animals. Hence, this study suggests that FU, a cytotoxic agent, may protect against MTX toxicity and improve its therapeutic index when FU administration precedes MTX or when these agents are given simultaneously. 相似文献
4.
Protection Against Chemically-Induced Oxidative Gastrointestinal Tissue Injury in Rats by Bismuth Salts 总被引:1,自引:0,他引:1
Debasis Bagchi Owen R. Carryl Minh X. Tran Manashi Bagchi Phillip J. Vuchetich Roger L. Krohn Siddhartha D. Ray Sekhar Mitra Sidney J. Stohs 《Digestive diseases and sciences》1997,42(9):1890-1900
Oxygen free radicals (OFR) are implicated in thepathogenesis of stress, chemically induced gastriclesions, and gastrointestinal injury. Theconcentration-dependent scavenging abilities of bismuthsubsalicylate (SBS), colloidal bismuth subcitrate (CBS), andselected OFR scavengers, including superoxide dismutase(SOD), catalase, mannitol, and allopurinol were examinedagainst biochemically or chemically generated superoxide anion, hydroxyl radical, andhypochlorite radical plus hypochlorous acid based on achemiluminescence assay. Furthermore, both gastric (GM)and intestinal mucosa (IM) were individually exposed in vitro to these free radical generatingsystems, and the concentration-dependent protectiveabilities of SBS and CBS against lipid peroxidation (LP)were compared with selected OFR scavengers. In addition, 24-hr fasted rats were orally treated with thenecrotizing agents 0.6 M HCl, 0.2 M NaOH, 80% ethanol,and aspirin (200 mg/kg). The extent of tissue injury inthe GM and IM was determined by assessing LP, DNA fragmentation, and membrane microviscosity.Dose- and time-dependent in vivo protective abilities ofCBS (100 mg/kg) and SBS (15 mg/kg) were also assessed.Following incubations with superoxide anion and hydroxyl radical generating systems in thepresence of 125 mg SBS/liter, approximately 47% and 61%inhibitions were observed in the chemiluminescenceresponse, respectively, while 48% and 46% inhibitions were observed with 125 mg CBS/liter. SBS andCBS exerted similar abilities towards hypochloriteradical plus hypochlorous acid. Approx. 3.1- and3.7-fold increases in LP were observed in the GM and IMof rats following oral administration of 0.6 MHCl. Pretreatment of the rats with SBS and CBS decreased0.6 M HCl-induced LP in the GM by approx. 39% and 27%,respectively, with similar decreases in LP in the IM. SBS exhibited better protectiveabilities towards 0.6 M HCl and 0.2 m NaOH-induced GMand IM injury as compared to CBS. SBS and CBS providedsimilar protection towards 80% ethanol-induced gastric injury, while CBS exerted a superior protectiveability towards aspirin-induced gastric injury. Theresults demonstrate that both SBS and CBS can scavengereactive oxygen species and prevent tissue damage produced by OFR. 相似文献
5.
Genetic diversity among clinical isolates of Acremonium strictum determined during an investigation of a fatal mycosis 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Journal of clinical microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Novicki TJ LaFe K Bui L Bui U Geise R Marr K Cookson BT 《Journal of clinical microbiology》2003,41(6):2623-2628
Primarily saprophytic in nature, fungi of the genus Acremonium are a well-documented cause of mycetoma and other focal diseases. More recently, a number of Acremonium spp. have been implicated in invasive infections in the setting of severe immunosuppression. During the course of routine microbiological studies involving a case of fatal mycosis in a nonmyeloablative hematopoietic stem cell transplant patient, we identified a greater-than-expected variation among strains previously identified as Acremonium strictum by clinical microbiologists. Using DNA sequence analysis of the ribosomal DNA intergenic transcribed spacer (ITS) regions and the D1-D2 variable domain of the 28S ribosomal DNA gene (28S), the case isolate and four other clinical isolates phenotypically identified as A. strictum were found to have <99% homology to the A. strictum type strain, CBS 346.70, at the ITS and 28S loci, while a sixth isolate phenotypically identified only as Acremonium sp. had >99% homology to the type strain at both loci. These results suggest that five out of the six clinical isolates belong to species other than A. strictum or that the A. strictum taxon is genetically diverse. Based upon these sequence data, the clinical isolates were placed into three genogroups. 相似文献
6.
Yang JQ Chun T Liu H Hong S Bui H Van Kaer L Wang CR Singh RR 《European journal of immunology》2004,34(6):1723-1732
Mechanisms responsible for the development of autoimmune skin disease in humans and animal models with lupus remain poorly understood. In this study, we have investigated the role of CD1d, an antigen-presenting molecule known to activate natural killer T cells, in the development of inflammatory dermatitis in lupus-susceptible MRL-lpr/lpr mice. In particular, we have established MRL-lpr/lpr mice carrying a germ-line deletion of the CD1d genes. We demonstrate that CD1d-deficient MRL-lpr/lpr mice, as compared with wild-type littermates, have more frequent and more severe skin disease, with increased local infiltration with mast cells, lymphocytes and dendritic cells, including Langerhans cells. CD1d-deficient MRL-lpr/lpr mice had increased prevalence of CD4(+) T cells in the spleen and liver and of TCR alpha beta (+)B220(+) cells in lymph nodes. Furthermore, CD1d deficiency was associated with decreased T cell production of type 2 cytokines and increased or unchanged type 1 cytokines. These findings indicate a regulatory role of CD1d in inflammatory dermatitis. Understanding the mechanisms by which CD1d deficiency results in splenic T cell expansion and cytokine alterations, with increased dermal infiltration of dendritic cells and lymphocytes in MRL-lpr/lpr mice, will have implications for the pathogenesis of inflammatory skin diseases. 相似文献
7.
G J Fourni M A Mignon-Cont J Lul M Gayral-Ta Minh S Haas R Bauriaud J J Cont 《Clinical and experimental immunology》1980,42(1):77-85
C57Bl/6 mice were injected intraperitoneally with 10(8) to 2 x 10(8) living K 38 Escherichia coli (E. coli) and serological changes and kidney involvement were studied. E. coli were found in the blood 45 min to 24 hr after injection. In serum, large amounts of deoxyribonucleic acid (DNA) were present 24 hr after E. coli injection, and thereafter disappeared. Seven days after infection, antibodies directed against E. coli, anti-DNA antibodies and C1q-binding substances were found in serum and the kinetics of the variations of these parameters were studied until day 35. Kidney lesions were evaluated immunochemically and by optical and electron microscopy. In the glomeruli, heavy granular deposits of IgG and IgM were constantly found in mesangium and along capillary walls. In most kidneys slight granular deposits of IgG and IgM were also found in the tubules. Histological studies revealed in the glomeruli mild endocapillary cell proliferation, focal thickening of glomerular basement membrane and dense deposits in mesangial and subendothelial areas and inside the glomerular basement membrane; in the tubules dense deposits were focally observed inside the tubular basement membrane. 相似文献
8.
Dunn GP Bruce AT Sheehan KC Shankaran V Uppaluri R Bui JD Diamond MS Koebel CM Arthur C White JM Schreiber RD 《Nature immunology》2005,6(7):722-729
'Cancer immunoediting' is a process wherein the immune system protects hosts against tumor development and facilitates outgrowth of tumors with reduced immunogenicity. Although interferon-gamma (IFN-gamma) is known to be involved in this process, the involvement of type I interferons (IFN-alpha/beta) has not been elucidated. We now show that, like IFN-gamma, endogenously produced IFN-alpha/beta was required for the prevention of the growth of primary carcinogen-induced and transplantable tumors. Although tumor cells are important IFN-gamma targets, they are not functionally relevant sites of the actions of the type I interferons. Instead, host hematopoietic cells are critical IFN-alpha/beta targets during development of protective antitumor responses. Therefore, type I interferons are important components of the cancer immunoediting process and function in a way that does not completely overlap the functions of IFN-gamma. 相似文献
9.
Choline acetyltransferase activity and cognitive domain scores of Alzheimer's patients 总被引:3,自引:0,他引:3
Choline acetyltransferase activity and cognitive domain scores of Alzheimer's patients. Item scores from the Mattis Dementia Rating Scale (MDRS) and the Mini-Mental State Examination (MMSE) from 389 patients with probable Alzheimer's disease were submitted to principal component analysis with orthogonal rotation. The optimal solution identified four factors that reflected the cognitive domains of attention/registration, verbal fluency/reasoning, graphomotor/praxis and recent memory. A subgroup of patients was identified for whom both the MDRS and the MMSE had been administered within the 12 months before death. Scores were assigned to these patients for the four factors. These cognitive-domain scores were then correlated with postmortem choline acetyltransferase (ChAT) activity in the medial frontal cortex, inferior parietal cortex, and hippocampus. ChAT activity in both the medial frontal and the inferior parietal cortex significantly correlated with scores on the graphomotor/praxis factor. Medial frontal ChAT also correlated significantly with the attention/registration scores. Hippocampal ChAT correlated significantly only with recent memory scores. These results are consistent with current animal research regarding the effect of selective cholinergic lesions on behavior. 相似文献
10.
Pham MT Maitz MF Reuther H Muecklich A Prokert F Steiner G 《Journal of biomedical materials research. Part A》2004,71(1):16-24
The native extracellular matrix (ECM) laid down on silicon and titanium surfaces by osteoblast-like SAOS-2 cells was exposed by selective removal of cells. This type of material surface ECM-Si, ECM-Ti was shown to promote the nucleation of calcium phosphate from a simulated body fluid (SBF). Microscopic and spectroscopic results revealed the effect was associated with a collagen fiber-free extracellular matrix. 相似文献