全文获取类型
收费全文 | 17936篇 |
免费 | 1396篇 |
国内免费 | 582篇 |
专业分类
耳鼻咽喉 | 76篇 |
儿科学 | 348篇 |
妇产科学 | 235篇 |
基础医学 | 2885篇 |
口腔科学 | 250篇 |
临床医学 | 1481篇 |
内科学 | 2782篇 |
皮肤病学 | 359篇 |
神经病学 | 1328篇 |
特种医学 | 297篇 |
外国民族医学 | 5篇 |
外科学 | 1692篇 |
综合类 | 1807篇 |
现状与发展 | 2篇 |
预防医学 | 813篇 |
眼科学 | 223篇 |
药学 | 2632篇 |
1篇 | |
中国医学 | 784篇 |
肿瘤学 | 1914篇 |
出版年
2023年 | 285篇 |
2022年 | 551篇 |
2021年 | 705篇 |
2020年 | 546篇 |
2019年 | 870篇 |
2018年 | 831篇 |
2017年 | 626篇 |
2016年 | 520篇 |
2015年 | 627篇 |
2014年 | 998篇 |
2013年 | 1056篇 |
2012年 | 859篇 |
2011年 | 954篇 |
2010年 | 877篇 |
2009年 | 784篇 |
2008年 | 786篇 |
2007年 | 743篇 |
2006年 | 684篇 |
2005年 | 569篇 |
2004年 | 555篇 |
2003年 | 456篇 |
2002年 | 393篇 |
2001年 | 310篇 |
2000年 | 268篇 |
1999年 | 272篇 |
1998年 | 233篇 |
1997年 | 193篇 |
1996年 | 188篇 |
1995年 | 124篇 |
1994年 | 114篇 |
1993年 | 112篇 |
1992年 | 115篇 |
1991年 | 103篇 |
1990年 | 84篇 |
1989年 | 84篇 |
1988年 | 85篇 |
1987年 | 81篇 |
1986年 | 91篇 |
1985年 | 265篇 |
1984年 | 357篇 |
1983年 | 232篇 |
1982年 | 221篇 |
1981年 | 189篇 |
1980年 | 165篇 |
1979年 | 142篇 |
1978年 | 123篇 |
1977年 | 87篇 |
1976年 | 119篇 |
1975年 | 98篇 |
1973年 | 62篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
21.
Katsuyoshi Habiro Hiroaki Shimmura Sakiko Kobayashi Motoko Kotani Yasuo Ishida Kazunari Tanabe Hiroshi Toma Ryo Abe 《American journal of transplantation》2005,5(4):702-711
Previously, we reported that allogeneic skin grafts were rapidly rejected by CD28 and CD40 ligand double deficient mice mediated by CD8+ T cells. These results indicated that some elements in addition to CD28- and CD40-mediated costimulation provide stimulatory signals for the activation of donor-specific CD8+ T cells. In this report, we investigated the role of inflammation associated with transplantation on costimulation-independent priming of CD8+ T cell during graft rejection. B6 RAG1 KO mice were transplanted with BALB/c-skin and adoptively transferred with syngeneic CD8+ T cells the same day or 50 days after transplantation. When blockade of CD28- and CD40-mediated costimulation failed to prevent acute rejection of freshly transplanted skin grafts, it efficiently delayed rejection of well-healed skin grafts. These results showed that factors associated with transplantation have essential roles in inducing costimulation blockade-resistant allograft rejection. Costimulation blockade failed to prevent acute graft-infiltration of NK cells and increasing expression of intragraft IL-12 and IL-15. These factors may trigger the graft-infiltration and priming of CD8+ T cells to induce costimulation blockade-resistant allograft rejection. 相似文献
22.
BRIAN J. STOCKMAN CAROL A. BANNOW ROBERT M. MICELI MICHAEL E. DEGRAAF H. DAVID FISCHER CLARK W. SMITH 《Chemical biology & drug design》1995,45(1):11-16
Epitope libraries provide a method to identify peptide ligands for antibodies, receptors or other binding proteins. As such, they provide a powerful tool to rapidly identify lead ligands in the drug discovery process. In an attempt to correlate structural information with the results from peptide screening, we have used NMR spectroscopy of peptide/antibody complexes to demonstrate that core residues identified through a two-stage selection process undergo a larger structural change upon binding antibody than do positions in the peptide amenable to a variety of side chains. The model system used was the M2 monoclonal antibody/Flag? octapeptide epitope system. We have analyzed two peptides: Ac-Asp-Tyr-Lys-Leu-Gly-Asp-Asp-Leu-NH2 (peptide l), which contains several non-core positions randomized, and Ac-Asp-Tyr-Lys-Asp-Asp-Asp-Asp-Leu-NH2 (peptide 2), which closely corresponds to the original Flag? sequence. Enrichment of the peptides with 15N facilitated the investigation by permitting spectral editing of the peptide resonances in the presence of antibody. For peptide 1 the absolute shifts for the free vs. Fab-bound peptide were found to be largest for the amide groups of Asp-1 and Asp-6, in agreement with classification of these residues as critical by the phage display library selection process. For peptide 2 the largest absolute shifts were observed for Asp-1 and Asp-4, with the other aspartic acid residues also showing significant but smaller changes. © Munksgaard 1995. 相似文献
23.
Kenichiro Mikawa Hiroaki Kume Kenzo Takagi 《Clinical and experimental pharmacology & physiology》1997,24(2):175-181
1. In order to examine the mechanisms of cGMP-induced relaxation in airway smooth muscle, the effects of atrial natriuretic peptide (ANP) and 8-brom cGMP on muscle tone were studied by measuring isometric tension, while the effects on cytosolic Ca2+ concentrations were studied by measuring the spectra of fura-2 loaded in guinea-pig tracheal strips. 2. Atrial natriuretic peptide and 8-brom cGMP caused a concentration-dependent inhibition of spontaneous tone in the guinea-pig trachea. The relaxant effects of these agents on spontaneous tone were markedly suppressed in the presence of iberiotoxin (IbTX), a selective inhibitor of large-conductance Ca2+-activated K+ (BKca) channels. Iberiotoxin (30 nmol/L) markedly affected the maximal effect induced by ANP and 8-brom cGMP and augmented EC70 values for ANP and EC50values for 8-brom cGMP approximately 27- and 17-fold, respectively. The inhibitory effects of IbTX on relaxation induced by these agents were diminished in the presence of 1 μmol/L nifedipine, an antagonist of voltage-operated Ca2+channels (VOCC). 3. The inhibitory action of ANP and 8-brom cGMP on spontaneous tone was not affected by the presence of 10 μmol/L glibenclamide, an inhibitor of ATP-sensitive K+ channels, and 100 nmol/L apamin, an inhibitor of small-conductance Ca2+-activated K+ channels. When these agents were applied to tissues precontracted by high (40mmol/L) K+, the relaxant effects of these agents markedly diminished. 4. The extracellular Ca2+-dependent contraction was inhibited in the presence of 0.3 μmoI/L ANP or 0.1 mmol/L 8-brom cGMP. Concentration—response curves to extracellular Ca2+ (0.03—2.4 mmol/L) were markedly diminished by exposure to these agents. The maximal effect induced by extracellular Ca2+ was affected by these agents. 5. Atrial natriuretic peptide caused an inhibition of spontaneous tone accompanied by a reduction in the intracellular Ca2+ concentration. In the presence of IbTX, the elimination of both muscle tone and cytosolic Ca2+ by ANP was suppressed. 6. We conclude that ANP and 8-brom cGMP activate BKca channels and that the inhibition of Ca2+ influx through VOCC, mediated by BKca channel activation, may be involved in cGMP-dependent bronchodilation. 相似文献
24.
Using the whole-cell configuration of the patch clamp technique, calcium-activated potassium currents (IK,Ca) were investigated in ramified murine brain macrophages. In order to induce IK,Ca the intracellular concentration of nominal free Ca2+ was adjusted to 1μM. The Ca2+-activated K+ current of brain macrophages did not show any voltage dependence at test potentials between –120 and +30mV. A tenfold change
in extracellular K+ concentration shifted the reversal potential of IK,Ca by 51mV. The bee venom toxin apamin applied at concentrations of up to 1μM did not affect IK,Ca. Ca2+-activated K+ currents of ramified brain macrophages were highly sensitive to extracellularly applied charybdotoxin (CTX). The half-maximal
effective concentration of CTX was calculated to be 4.3nM. In contrast to CTX, the scorpion toxin kaliotoxin did not inhibit
IK,Ca at concentrations between 1 and 50nM. Tetraethylammonium (TEA) blocked 8.0% of IK,Ca at a concentration of 1mM, whereas 31.4% of current was blocked by 10mM TEA. Several inorganic polyvalent cations were tested
at a concentration of 2mM for their ability to block IK,Ca. La3+ reduced IK,Ca by 72.8%, whereas Cd2+ decreased IK,Ca by 17.4%; in contrast, Ni2+ did not have any effect on IK,Ca. Ba2+ applied at a concentration of 1mM reduced IK,Ca voltage-dependently at hyperpolarizing potentials.
Received: 17 January / Accepted: 5 May 1997 相似文献
25.
Abstract: We analyzed the expression of CEA, CA19-9, CA125, CA15-3 (DF3), PCNA and p53 immunohistochemically in 14 tissue specimens of mucosal cancers in adenoma, seven tubulovillous adenoma specimens, and 16 tubular adenoma specimens. The rates of positive staining for mucosal cancer in adenoma, tubulovillous adenoma and tubular adenoma specimens, respectively, were: for CEA: 100%, 85.7% and 75%; for CA19-9: 71.4%, 71.4% and 56.2%; for CA125:0%, 0% and 0%;for CA15-3 (DF3): 64.3 %, 0% and 0 %; for PCNA: 100%, 88.9% and 56.2%; and for p53: 35.7%, 0% and 0% . The results suggest that the expressions of CEA, CA19-9, CA15-3 (DF3), PCNA and p53 are related to colorectal tumorigenesis. None of the specimens studied showed staining for CA125, suggesting that CA125 is not involved in the early stages of colorectal carcinogenesis. There was no significant difference in the rates of positive staining for CEA and CA19-9 among mucosal cancer in adenoma, tubular adenoma and tubulovillous adenoma specimens. However, the rates of positive staining for PCNA and p53 were significantly higher in mucosal cancer in adenoma specimens than for tubular adenoma specimens (p<0.05), and the rate of CA15-3 (DF3) positive staining was significantly higher for mucosal cancer in adenoma than for tubulovillous adenoma (p<0.01) and tubular adenoma (p< 0.001) specimens. Therefore, the CA15-3 (DF3) antigen is an immunohistochemical marker for colorectal carcinomas. The present results suggest that CA15-3 (DF3), PCNA and p53 play important roles in the genesis of colorectal adenomas. 相似文献
26.
曾艺东 《白求恩军医学院学报》2005,3(3):137-138
目的观察喜炎平与维生素K3联合治疗小儿秋季腹泻的疗效.方法将89例秋季腹泻患儿随机分为2组.治疗组采用喜炎平与维生素K3联合治疗,对照组则采用利巴韦林治疗,疗程5d.结果治疗组的总有效率为93.3%,显著优于对照组的65.9%(X2=10.37,P<0.01).结论喜炎平与维生素K3联合治疗小儿秋季腹泻值得进一步推广. 相似文献
27.
L. Elghazi L. Rachdi A. J. Weiss C. Cras-Méneur E. Bernal-Mizrachi 《Diabetes, obesity & metabolism》2007,9(S2):147-157
The insulin receptor substrate-2/phosphoinositide 3-kinase (PI3K) pathway plays a critical role in the regulation of β-cell mass and function, demonstrated both in vitro and in vivo . The serine threonine kinase Akt is one of the promising downstream molecules of this pathway that has been identified as a potential target to regulate function and induce proliferation and survival of β cells. Here we summarize some of the molecular mechanisms, downstream signalling pathways and critical components involved in the regulation of β-cell mass and function by Akt. 相似文献
28.
A. Lecci F. Borsini L. Gragnani G. Volterra A. Meli 《Journal of neural transmission (Vienna, Austria : 1996)》1991,83(1-2):67-76
Summary Stress-induced hyperthermia (SIH), which is seen in the last mice removed from the cage, is a novel animal model sensitive to anxiolytic drugs. SIH is antagonized by CL 218872 (25 and 50 mg/kg, os), by tracazolate (5 and 7.5 mg/kg, ip) and by 2-AP-5 (50 and 100 mg/kg, ip). At higher dose, CL 218872 (100 mg/kg, os) and tracazolate (12.5 mg/kg, ip) lose their activity.PK 9084 (5–40 mg/kg, ip) and CGS 9896 (2–20 mg/kg, both ip and os) were also ineffective in preventing SIH. The anti-hyperthermic effect of CL 218872 (25 mg/kg) and tracazolate (7.5 mg/kg) was blocked by the benzodiazepine antagonist Ro 15–1788 (15 mg/kg). CGS 9896 (10 mg/kg, os) also reversed the effect of CL 218872 (25 mg/kg) on SIH.Differently from anxiolytics, MK-801 (0.5–1 mg/kg, os), PCP (2.5 mg/kg, ip) and d-amphetamine (10 mg/kg, ip) evoked hyperthermia in the first set of mice and prevented a further stress-induced rise of body temperature in the last set of mice. 相似文献
29.
P Mismetti S Laporte P Zufferey M Epinat H Decousus M Cucherat 《Journal of thrombosis and haemostasis》2004,2(7):1058-1070
BACKGROUND: The benefit-to-risk ratio of vitamin K antagonists (VKA), relative to active comparators, especially low-molecular-weight heparins (LMWH), for preventing venous thromboembolism in patients undergoing major orthopedic surgery is debated. OBJECTIVES: We performed a meta-analysis of all randomized trials in orthopedic surgery comparing adjusted doses of VKA to control treatments. PATIENTS AND METHODS: An exhaustive literature search, both manual and computer-assisted, was performed. Studies were selected on the basis of randomization procedure (VKA vs. a control group). At least one of the following outcome measures was to be evaluated: deep vein thrombosis (DVT), pulmonary embolism (PE), death, major hemorrhage or wound hematoma. Four reviewers assessed each article to determine eligibility for inclusion and outcome measures. RESULTS: VKAs were more effective than placebo or no treatment in reducing DVT [567 patients, relative risk (RR) = 0.56, 95% confidence interval (CI) 0.37, 0.84, P < 0.01] and clinical PE (651 patients, RR = 0.23, 95% CI 0.09, 0.59, P < 0.01). These results were obtained at the cost of a higher rate of wound hematoma (162 patients, RR = 2.91, 95% CI 1.09, 7.75, P = 0.03). VKAs were also more effective than intermittent pneumatic compression (534 patients, RR = 0.46, 95% CI 0.25, 0.82, P = 0.009) in preventing proximal DVT. In contrast, VKAs were less effective than LMWH in preventing total DVT and proximal DVT (9822 patients, RR = 1.51, 95% CI 1.27, 1.79, P < 0.001; and 6131 patients, RR = 1.51, 95% CI 1.04, 2.17, P = 0.028, respectively). The differences between VKA and LMWH in major hemorrhage and wound hematoma were not significant. CONCLUSIONS: In patients undergoing major orthopedic surgery, VKAs are less effective than LMWH, without any significant difference in the bleeding risk. 相似文献
30.
Keiichiro Yoshinaga Chietsugu Katoh Kazuyuki Noriyasu Yasuyoshi Iwado Hideto Furuyama Yoshinori Ito Yuji Kuge Tetsuro Kohya Akira Kitabatake Nagara Tamaki 《Journal of nuclear cardiology》2003,10(3):275-283
BACKGROUND: Myocardial perfusion single photon emission computed tomography (SPECT) occasionally fails to detect coronary stenosis in patients with coronary artery disease (CAD). We evaluated coronary flow reserve (CFR) using oxygen 15-labeled water in areas with and without ischemia on technetium 99m tetrofosmin stress perfusion SPECT in patients with angiographically documented CAD. METHODS AND RESULTS: Twenty-seven patients with CAD and eleven age-matched normal subjects were studied. Baseline myocardial blood flow (MBF) and MBF during hyperemia induced by intravenous adenosine triphosphate infusion (0.16 mg. kg(-1). min(-1)) were determined with the use of O-15-labeled water positron emission tomography, and the CFR was calculated. Tc-99m tetrofosmin stress/rest SPECT was performed for comparison. On the basis of the results of coronary angiography and SPECT, coronary segments were divided into 3 types: segments with coronary stenosis and a perfusion abnormality on stress SPECT imaging (group A, n = 16), segments with coronary stenosis without a perfusion abnormality (group B, n = 42), and remote segments with no coronary stenosis or perfusion abnormality (group C, n = 18). Baseline MBF values were similar among the 3 groups. CFR in group A was lower (1.82 +/- 0.54) than in group B (2.22 +/- 0.87, P <.05), in group C (2.92 +/- 1.21, P <.01), and in normal segments (3.86 +/- 1.24, P <.001). CFR in group B was lower than in group C (P <.02) and in normal segments (P <.001). CFR in group C was lower than in normal segments (P <.02). CONCLUSIONS: Areas with a perfusion abnormality on stress SPECT had reduced CFR. In the areas without a perfusion abnormality and with coronary stenosis, lowering of CFR was intermediate between the areas with a perfusion abnormality and remote segments. Moreover, CFR was slightly, but significantly, lower in remote segments in patients with CAD compared with normal segments. 相似文献