全文获取类型
收费全文 | 174644篇 |
免费 | 10508篇 |
国内免费 | 443篇 |
专业分类
耳鼻咽喉 | 2264篇 |
儿科学 | 5638篇 |
妇产科学 | 3675篇 |
基础医学 | 23875篇 |
口腔科学 | 7766篇 |
临床医学 | 12875篇 |
内科学 | 39217篇 |
皮肤病学 | 4432篇 |
神经病学 | 14662篇 |
特种医学 | 5347篇 |
外国民族医学 | 26篇 |
外科学 | 21371篇 |
综合类 | 1407篇 |
现状与发展 | 1篇 |
一般理论 | 63篇 |
预防医学 | 18204篇 |
眼科学 | 3221篇 |
药学 | 10782篇 |
中国医学 | 721篇 |
肿瘤学 | 10048篇 |
出版年
2023年 | 883篇 |
2022年 | 2020篇 |
2021年 | 3873篇 |
2020年 | 2575篇 |
2019年 | 3622篇 |
2018年 | 5014篇 |
2017年 | 3762篇 |
2016年 | 3533篇 |
2015年 | 4117篇 |
2014年 | 5655篇 |
2013年 | 7136篇 |
2012年 | 11041篇 |
2011年 | 11545篇 |
2010年 | 5842篇 |
2009年 | 5212篇 |
2008年 | 8867篇 |
2007年 | 9488篇 |
2006年 | 8793篇 |
2005年 | 9021篇 |
2004年 | 8478篇 |
2003年 | 7734篇 |
2002年 | 5764篇 |
2001年 | 4984篇 |
2000年 | 4987篇 |
1999年 | 4371篇 |
1998年 | 1560篇 |
1997年 | 1297篇 |
1996年 | 1281篇 |
1995年 | 1085篇 |
1994年 | 1079篇 |
1993年 | 984篇 |
1992年 | 2674篇 |
1991年 | 2573篇 |
1990年 | 2353篇 |
1989年 | 2344篇 |
1988年 | 2120篇 |
1987年 | 1962篇 |
1986年 | 1840篇 |
1985年 | 1768篇 |
1984年 | 1267篇 |
1983年 | 1020篇 |
1982年 | 575篇 |
1981年 | 516篇 |
1980年 | 497篇 |
1979年 | 930篇 |
1978年 | 616篇 |
1977年 | 485篇 |
1975年 | 548篇 |
1974年 | 551篇 |
1973年 | 546篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
991.
F. G. Roberge Y. de Kozak T. Utsumi J. P. Faure R. B. Nussenblatt 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》1989,227(1):67-71
It has been proposed that the introduction of foreign material into the eye at the moment of a penetrating trauma provides an adjuvant effect which, coupled with the release of antigen, might be responsible for sensitizing the immune system to produce a contralateral sympathetic ophthalmia. We addressed that hypothesis by injecting S-antigen with complete Freund's adjuvant (CFA) into the anterior chamber (AC) of the eye of Lewis rats. The injection of an identical dose of antigen (30 g S-Ag in CFA in a total volume of 10 l) via the foodpad (FP) or under the conjunctiva (SC) could induce typical experimental autoimmune uveitis (EAU). By immunizing via the AC route, we could demonstrate a positive sensitization of the immune system, manifested by serum antibody production against S-Ag and by the presence of S-Ag-specific, responsive T-lymphocytes in the spleen. However, immunization via the AC route did not induce contralateral uveitis, and the animals did not produce a DTH skin response when challenged intradermally with S-Ag as they did after FP immunization. In the light of these results, we evaluated the possibility that a DTH suppressive response was elicited by intracameral (IC) injection as seen in anterior chamber-associated immune deviation (ACAID): we tested the effect of splenectomy and cyclophosphamide pretreatment before IC immunization and the effect of secondary footpad immunization as well as T-helper cell transfer after IC immunization. The results given by these approaches argue against the induction of suppressor cells by IC immunization. We believe that the absence of lymphatic drainage from the interior of the eye is probably responsible for the absence of EAU induction through the IC route and that extrusion of the antigen under the conjunctiva might be required for the activation of EAU effector cells. 相似文献
992.
M. H. de Vries F. A. M. Redegeld A. Sj. Koster J. Noordhoek J. G. de Haan R. P. J. Oude Elferink P. L. M. Jansen 《Naunyn-Schmiedeberg's archives of pharmacology》1989,340(5):588-592
Summary Recently, a mutant rat strain was described with a genetic defect for the biliary excretion of organic anions (TR– rats). To determine the possible heterogeneity of the transport systems in liver, intestine and kidney we investigated the transport of the anion 1-naphthol--d-glucuronide (1-NG) in isolated vascularly perfused organ preparations of the rat liver, intestine and kidney of both Wistar rats and TR– rats. 1-NG was administered as such (liver and kidney experiments) or formed intracellularly from 1-naphthol (1-N) (liver and gut experiments). Independent of the type of exposure to 1-NG, the biliary excretion was considerably impaired in TR– rats. In the intestine the total appearance and the vascular/luminal distribution pattern of 1-NG were not significantly different from the values in control rats. Furthermore, no significant disturbance was found with respect to the renal clearance of 1-NG in the TR– rat when compared with the Wistar rat. Thus, the genetic defect in the TR– rat is restricted to an impaired hepatobiliary excretion of 1-NG and does not affect the excretory systems of the intestine and kidney. These results suggest that the excretion of 1-NG by the liver, intestine and kidney involves distinct organ-specific transport systems. 相似文献
993.
M. H. de Vries G. A. Hofman A. Sj. Koster J. Noordhoek 《Naunyn-Schmiedeberg's archives of pharmacology》1989,340(2):239-245
Summary Using the isolated vascularly fluorocarbon emulsion perfused rat small intestine some factors which determine the extent of the intestinal glucuronidation of 1-naphthol to 1-naphthol--d-glucuronide were studied. Increasing the luminal 1-naphthol concentration resulted in a concomitant increase in the 1-naphthol appearance in the vascular perfusate. In contrast, the total appearance of 1-naphthol--d-glucuronide increased less than proportional to the increase in the luminal 1-naphthol concentration. About 88% of the total amount of 1-naphthol--d-glucuronide excreted was released into the vascular perfusate. The capacity-limited intestinal glucuronide efflux is most likely due to saturation of the excretory mechanism for 1-naphthol--d-glucuronide. Decreasing the vascular flow rate influenced both the appearance of 1-naphthol and 1-naphtol--d-glucuronide in the vascular perfusate, whereas the appearance of 1-naphthol--d-glucuronide in the luminal perfusate was essentially flow-independent. A noradrenaline-induced change in the haemodynamic state of the vascular bed (with the total flow kept constant) resulted in a marked decrease in the 1-naphthol vascular concentration. The vascular 1-naphthol--d-glucuronide concentration was only slightly affected. These results indicate that changes in blood flow and blood flow distribution within the intestinal wall can affect the extent of presystemic intestinal metabolism by interfering with the absorption of the parent compound and the efflux of formed conjugates. These parameters can be of paramount importance for causing variable intestinal first-pass effects of drugs in vivo.
Send offprint requests to M. H. de Vries at the above address 相似文献
994.
van de Poll Monique L.M.; van der Hulst Dolinda A.M.; Tates Ad D.; Mulder Gerard J.; Meerman John H.N. 《Carcinogenesis》1989,10(4):717-722
N-Hydroxy-Z-acetylaminofluorene (N-OH-AAF) was administeredi.p. to male Wistar rats 17 h after partial hepatectomy. Hepatocyteswere analyzed for the presence of micronuclei 7 h, 1, 2, 3 and4 days after injection. N-OH-AAF treatment resulted in a highfrequency of micronucleated hepatocytes at days 3 and 4 (19.5and 19.6 respectively). The frequency of micronucleated hepatocyteswas not increased above control values when hepatocytes wereisolated as early as 7 h, 1 or 2 days after injection. Pretreatmentwith the sulfotransferase inhibitor pentachlorophenol (PCP)45 min before injection of N-OH-AAF almost completely preventedthe formation of micronuclei by N-OH-AAF. Parallel biochemicalstudies indicated that inhibition of sulfation of N-OH-AAF byPCP pretreatment prevented the formation of the N-acetylatedDNA adducts iV-deoxyguanosin-8-yl-AAF and 3-deoxyguanosin-N2-yl-AAFby {small tilde}85%. Total adduct formation to DNA was, however,not lowered because of an increase in the formation of the deacetylatedadduct, N-deoxy-guanosin-8-yl-AAF. The lower frequency of micronucleatedhepatocytes observed in the group pretreated with PCP, did notresult from less proliferative activity in this group as comparedto the group treated with N-OH-AAF alone. Therefore, the decreasein the formation of micronuclei indicates that PCP preventsthe clastogenic damage caused by N-OH-AAF. It is concluded thatthe clastogenicity of N-OH-AAF in rat liver is related to theformation of N-acetylated DNA adducts (i.e. N-deoxyguanosin-8-yl-AAFand/or 3-deoxy-guanosin-N2-yl-AAF) and is not related to theformation of the deacetylated DNA adduct N-deoxyguanosin-8-yl-AF. 相似文献
995.
J S Coon A D Deitch R W de Vere White L G Koss M R Melamed J E Reeder R S Weinstein R P Wersto L L Wheeless 《Cancer》1989,63(8):1592-1599
The National Cancer Institute's Flow Cytometry Network (NCI-FCN) is attempting to facilitate the transfer of flow cytometry (FCM) of exfoliated bladder cells from the research laboratory to the clinical laboratory. Demonstrating interinstitutional consistency in FCM analysis of replicate specimens simulating clinical barbotage specimens, fixed to allow easy transportation and storage at room temperature was one specific objective. Simulated barbotage specimens were prepared by mixing cultured aneuploid bladder carcinoma cells with normal or mitogen-stimulated peripheral blood mononuclear cells in different ratios. The samples were fixed in 10% formalin for 30 minutes, stored in buffer, and enucleated with pepsin, pH 1.5, before staining with propidium iodide for FCM DNA analysis. Preservation in ethanol or other common DNA cytochemical reagents was found to be unsatisfactory. In contrast, the formalin-fixed samples showed excellent preservation of quantitative DNA fluorescence and coefficient of variation of histogram peaks for over 2 weeks. Exchange of eight fixed specimens among five network laboratories that analyzed them as "unknowns" showed good overall agreement on histogram data and interpretation, although some noteworthy interlaboratory differences were found. This technique could be used for self-assessment surveys of clinical laboratory performance in DNA FCM of bladder barbotage specimens. 相似文献
996.
Joost B. M. M. van Bree Anne V. Baljet Anton van Geyt Albertus G. de Boer Meindert Danhof Douwe D. Breimer 《Journal of pharmacokinetics and pharmacodynamics》1989,17(4):441-462
The unit impulse response theory has been adapted to characterize the transport profile of drugs into the central nervous system (CNS). From the obtained input function, the cumulative plasma volume (V) cleared by transport into the CNS in time can be calculated. Simulation studies demonstrated that transport governed by passive diffusion resulted in a linear relationship between V and time, while the slope of the line, the blood- brain barrier (BBB) clearance, proved to be an adequate and model independent parameter to characterize drug transport into the CNS. The error in the result of the numerical procedure could be limited to less than 10% of the theoretically predicted value. Superposition of 5 or 10% random noise on simulated data did not result in significant differences between the calculated and theoretically predicted clearance values. Simulations of carrier-mediated transport resulted in nonlinear transport curves; the degree of nonlinearity, and thus the detectability, was dependent on the initial degree of saturation of the system, the rate of desaturation, as caused by drug elimination processes and the noise level on the data. In vivoexperiments in the rat were performed, using atenolol, acetaminophen, and antipyrine as model drugs. Linear transport relationships were obtained for all drugs, indicating that transport was dependent on passive diffusion or a low affinity carrier system. BBB- clearance values were 7±1 l/min for atenolol, 63±7 ul/min for acetaminiphen and 316±25 l/min for antipyrine. These experiments validate the applicability of the presented technique in in vivostudies. 相似文献
997.
Edmundo Ferreol Raymond Sawayal Gabrielle M. de Courten-Myers 《Journal of neuro-oncology》1989,7(2):121-128
Summary We report a case of a third ventricular neuroblastoma (neurocytoma) in a 66 year old man. A stereotactic needly biopsy was performed to obtain a tissue diagnosis and was followed by total resection. We elected not to give radiation or chemotherapy and to follow the patient closely with serial CT scans. Presently, 48 months postoperatively, the patient is free of tumor by head CT scan and able to live independently. We reviewed the literature of primary cerebral neuroblastomas/neurocytomas occurring in adults (15 years of age) and found 32 cases. Our patient is the oldest of this group with a mean age of 32 ± 14 years (S.D.). The location of the 33 neoplasms was intraventricular in 17 cases (52%) and intraparenchymal in 16 cases. The male to female ratio was 2: 1. Of the 17 patients having a minimal follow-up period of 5 months (mean 51 months), five developed recurrences after 5 to 144 months (mean 50 months) compared to 12 patients without recurrence after a 6- to 72-month follow-up period (mean 52 months). Recurrences occurred statistically significantly more often in parenchymal neuroblastomas/neurocytomas than in intraventricular tumor locations. 相似文献
998.
van Hoogdalem Ewoud J. Heijligers-Feijen Cornelia D. de Boer Albertus G. Verhoef J. Coos Breimer Douwe D. 《Pharmaceutical research》1989,6(1):91-95
The stability of the neuroleptic peptide des-enkephalin--endorphin (DEE; Org 5878) in the rectal lumen and the rectal bioavailability of DEE were investigated in conscious rats. Furthermore, the influence of peptidase inhibition, peptidase saturation, and absorption enhancement on DEE bio-availability were evaluated. Na2EDTA (0.25%, w/v) prolonged the degradation half-life of DEE in the ligated colon from 33 ± 7 to 93 ± 45 min. Without adjuvant, tritium-labeled DEE was absorbed from the rat rectum to a very low extent (0–4%). After administration of an excess of unlabeled DEE or with Na2EDTA, comparable results were obtained. The medium-chain glyceride preparation MGK markedly enhanced the rectal DEE bioavailability, up to 8–20%, which was further increased to 10–44% by coadministration of Na2EDTA. No substantial influence of varying the rectal delivery rate was observed. The results suggest that absorption enhancement and enzyme inhibition both are essential for effective increase of rectal peptide bioavailability. 相似文献
999.
Clinical characterization of non-small-cell lung cancer tumors showing neuroendocrine differentiation features 总被引:4,自引:0,他引:4
H H Berendsen L de Leij S Poppema P E Postmus A Boes H J Sluiter H The 《Journal of clinical oncology》1989,7(11):1614-1620
In most cases of small-cell lung carcinomas (SCLC) phenotypic features compatible with a neuroendocrine differentiation status can be identified by monoclonal (MOC) antibody-based immunohistological procedures. Similar features can be recognized only in a minority of non-SCLC tumors. During a period of 30 months, all diagnostic non-SCLC biopsies (141 cases) were prospectively analysed for the presence of markers indicative for neuroendocrine differentiation. In 31% of all cases, such a presence could be noticed. Neuroendocrine differentiation (50% to 100% positive-staining tumor cells) was recognized more frequently in adenocarcinoma when compared to large-cell and squamous-cell carcinoma (chi 2 = 9.31, 2 degrees of freedom, P less than 0.01). To investigate whether the clinical behavior of these "neuroendocrine" non-SCLC cases mimics SCLC, a multivariate analysis for prognostic factors was performed. Among other prognostic factors, biopsies containing more than 50% positive-staining tumor cells with the MOC antibody-1 (MOC-1) were recognized as negative prognostic factors. 相似文献
1000.
de Novellis V Mariani L Palazzo E Vita D Marabese I Scafuro M Rossi F Maione S 《Neuroscience》2005,134(1):269-281
This study was undertaken to analyze the involvement of periaqueductal gray (PAG) cannabinoid or group I metabotropic glutamate receptors in the formalin-induced changes on the rostral ventromedial medulla (RVM) ON- and OFF-cells activities. S.c. injection of formalin into the hind paw produced a transient decrease (4-6 min) followed by a longer increase (25-35 min) in tail flick latencies. Formalin also increased basal activity in RVM ON-cells (42+/-7%) and decreased it in OFF-cells (35+/-4%). Intra-PAG microinjection of (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate (WIN 55,212-2) (2 nmol/rat), a cannabinoid receptor agonist, prevented the formalin-induced changes in RVM cell activities. Higher dosages of WIN 55,212-2 (4-8 nmol/rat) increased the tail flick latencies, delayed the tail flick-related onset to ON-cell burst, and decreased the duration of OFF-cell pause. Furthermore, WIN 55,212-2 at a dosage of 8 nmol/rat decreased RVM ON-cell (57+/-7%) and increased OFF-cell ongoing activities (26+/-4%). These effects were prevented by N-piperidino-5-(4-chlorophenyl)-1-(2,4dichlorophenyl)-4-methyl-3-pyrazolecarboxamide SR141716A, (1 pmol/rat), a CB1 cannabinoid receptor antagonist, or by 2-methyl-6-(phenylethynyl)pyridine (MPEP 20 nmol/rat), a selective mGlu5 glutamate receptor antagonist. T7-(hydroxyimino) cyclopropa[b]chromen-1alpha-carboxylate ethyl ester (CPCOOE/50 nmol/rat) and (S)-(+)-alpha-amino-4-carboxy-2-methylbenzeneacetic acid (LY367385, 20 nmol/rat), selective mGlu1 glutamate receptor antagonists, were ineffective in preventing the WIN-induced effects. This study suggests that s.c. injection of formalin modifies RVM neuronal activities and this effect is prevented by PAG cannabinoid receptor stimulation. Moreover, the physiological stimulation of PAG mGlu5, but not mGlu1 glutamate receptors, seems to be required for the cannabinoid-mediated effect. 相似文献