全文获取类型
收费全文 | 175397篇 |
免费 | 10538篇 |
国内免费 | 444篇 |
专业分类
耳鼻咽喉 | 2291篇 |
儿科学 | 5611篇 |
妇产科学 | 3675篇 |
基础医学 | 23784篇 |
口腔科学 | 8029篇 |
临床医学 | 12897篇 |
内科学 | 39349篇 |
皮肤病学 | 4456篇 |
神经病学 | 14703篇 |
特种医学 | 5455篇 |
外国民族医学 | 26篇 |
外科学 | 21600篇 |
综合类 | 1409篇 |
现状与发展 | 1篇 |
一般理论 | 64篇 |
预防医学 | 18201篇 |
眼科学 | 3244篇 |
药学 | 10794篇 |
中国医学 | 731篇 |
肿瘤学 | 10059篇 |
出版年
2023年 | 923篇 |
2022年 | 2025篇 |
2021年 | 3769篇 |
2020年 | 2501篇 |
2019年 | 3585篇 |
2018年 | 5015篇 |
2017年 | 3748篇 |
2016年 | 3506篇 |
2015年 | 4095篇 |
2014年 | 5607篇 |
2013年 | 7108篇 |
2012年 | 10989篇 |
2011年 | 11488篇 |
2010年 | 5902篇 |
2009年 | 5260篇 |
2008年 | 8889篇 |
2007年 | 9501篇 |
2006年 | 8819篇 |
2005年 | 9103篇 |
2004年 | 8534篇 |
2003年 | 7783篇 |
2002年 | 5819篇 |
2001年 | 5107篇 |
2000年 | 5077篇 |
1999年 | 4469篇 |
1998年 | 1585篇 |
1997年 | 1317篇 |
1996年 | 1302篇 |
1995年 | 1105篇 |
1994年 | 1083篇 |
1993年 | 988篇 |
1992年 | 2691篇 |
1991年 | 2642篇 |
1990年 | 2389篇 |
1989年 | 2390篇 |
1988年 | 2154篇 |
1987年 | 1998篇 |
1986年 | 1861篇 |
1985年 | 1792篇 |
1984年 | 1284篇 |
1983年 | 1025篇 |
1982年 | 580篇 |
1981年 | 521篇 |
1980年 | 511篇 |
1979年 | 928篇 |
1978年 | 614篇 |
1977年 | 484篇 |
1975年 | 554篇 |
1974年 | 559篇 |
1973年 | 553篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
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
992.
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
993.
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
994.
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
995.
van Sighem A Danner S Ghani AC Gras L Anderson RM de Wolf F;ATHENA National Observational Cohort Study 《Journal of acquired immune deficiency syndromes (1999)》2005,40(2):212-218
Mortality in HIV-infected patients has decreased dramatically since the introduction of highly active antiretroviral therapy (HAART). We analyzed progression to death in a population of 3678 antiretroviral treatment-naive patients from the ATHENA national observational cohort from 24 weeks after the start of HAART. Mortality was compared with that in the general population in the Netherlands matched by age and gender. Only log-transformed CD4 cell count (hazard ratio [HR] = 0.50, 95% confidence interval [CI]: 0.40 to 0.61 per unit increase) and plasma viral load (HR = 0.30, 95% CI: 0.15 to 0.60, HIV RNA level <100,000 vs. > or = 100,000 copies/mL) measured at 24 weeks and infection via intravenous drug use (IDU) (HR = 0.16, 95% CI: 0.10 to 0.26, non-IDU vs. IDU) were significantly associated with progression to death. For non-IDU patients with 600 x 10 CD4 cells/L and an HIV RNA level <100,000 copies/mL at 24 weeks, mortality was predicted to be 5.3 (95% CI: 3.5 to 8.4) and 10.4 (95% CI: 6.4 to 17.4) times higher than in the general population for 25-year-old men and women, respectively, and 1.15 (95% CI: 1.08 to 1.25) and 1.29 (95% CI: 1.16 to 1.50) times higher for 65-year-old men and women, respectively. Hence, mortality in HIV-infected patients with a good initial response to HAART is still higher than in the general population. 相似文献
996.
为探讨单链抗体 (ScFv )对重症肌无力 (MG )的特异性免疫治疗作用 ,从分离自MG患者胸腺的抗乙酰胆碱受体(AchR )抗原结合片段Fab6 37构建单链抗体ScFv6 37。应用放射免疫测定法测定了ScFv6 37与刺激抗原人AchR的特异性结合活性以及与相关抗原大鼠AchR和电鳐AchR的交叉反应 ,应用竞争性ELISA测定抑制致病性抗AchR完整抗体IgG6 37与人AchR结合活性。结果发现ScFv6 37只能与人AchR结合 ,不能与大鼠和电鳐的AchR结合。对IgG6 37与人AchR结合的抑制率为 17 5 %~ 32 9%。表明单链抗体对AchR具有一定的“保护”作用。 相似文献
997.
Thomazi AP Godinho GF Rodrigues JM Schwalm FD Frizzo ME Moriguchi E Souza DO Wofchuk ST 《Mechanisms of ageing and development》2004,125(7):475-481
The excitotoxicity of the neurotransmitter glutamate has been shown to be connected with many acute and chronic diseases of the CNS. High affinity sodium-dependent glutamate transporters play a key role in maintaining adequate levels of extracellular glutamate. In the present study, we used slices of striatum, hippocampus and cortex from rat brain to describe the in vitro profile of glutamate uptake during development and ageing, and its sensitivity to guanosine. In all structures, glutamate uptake was higher in immature animals. There was a maximum decrease in glutamate uptake in striatum and hippocampus in 15-month-old rats, which later increased, while in cortex there was a significant decrease in rats aged 60 days old. The effect of guanosine seems to be age and structure dependent since the increase in basal glutamate uptake was only seen in slices of cortex from 10-day-old animals. 相似文献
998.
Ringrose JH Meiring HD Speijer D Feltkamp TE van Els CA de Jong AP Dankert J 《Infection and immunity》2004,72(9):5097-5105
Reactive arthritis (ReA) induced by infection with several gram-negative bacteria is strongly associated with expression of the major histocompatibility complex class I molecule HLA-B27. It is thought that due to the intracellular lifestyle of ReA-inducing bacteria, bacterial fragments can be presented by HLA-B27. Cytotoxic T cells recognizing such bacterial peptides or other induced host peptides could cross-react with self peptides presented in the joints, giving rise to disease. Studies to analyze the B27 peptide repertoire in relation to infection were severely hampered, as complex peptide profiles obtained from separate infected and noninfected cell preparations had to be compared. For this study, we applied a new approach to examine the effect of Salmonella enterica serovar Typhimurium infection on the B27 peptide repertoire presented by the HLA-B*2704 subtype associated with disease. Firstly, we showed that both host cell and S. enterica serovar Typhimurium proteins can be tagged metabolically with stable-isotope-labeled arginine. We then designed experiments so that either the tagged endogenous or tagged bacterial B*2704-presented peptide repertoires from infected cells could be analyzed by mass spectrometry from single peptide preparations that included uninfected controls. Using this new approach, we found no evidence for significant changes in endogenous B*2704 peptide presentation after infection or for any S. enterica serovar Typhimurium-derived B27-bound peptide. In conclusion, the hypothesis that S. enterica serovar Typhimurium induces changes in B27 peptide presentation could not be supported. 相似文献
999.
Lima JO dos Santos JK Pereira JF de Resende ML de Araújo EF de Queiroz MV 《Current genetics》2003,42(4):236-240
Protoplasts of the pathogenic plant fungus, Crinipellis perniciosa, were transformed to hygromycin B resistance using the pAN7-1 plasmid, which contains the Escherichia coli hph gene under the control of Aspergillus nidulans regulatory sequences. The pAN7-1 plasmid was introduced by PEG/CaCl(2) treatment. Transformation frequencies of 1.6-2.5 transformants/microg of DNA were achieved. About 54% of the transformants were abortive and 40 analyzed transformants were mitotically stable and showed different hygromycin B resistance levels. The presence of the hph gene was checked by PCR in five transformants and the integration of multiple plasmid copies into different genome sites was observed by Southern analysis. This is the first report of a C. perniciosa transformation system and represents an important step for further research into genetic manipulation of this fungal plant pathogen. 相似文献
1000.
Daher A de Boer WI El-Marjou A van der Kwast T Abbou CC Thiery JP Radvanyi F Chopin DK 《Laboratory investigation; a journal of technical methods and pathology》2003,83(9):1333-1341
Members of the epidermal growth factor (EGF) family and their receptors are involved in many cellular processes, including proliferation, migration, and differentiation. We have previously reported that these growth factors are expressed and have specific regulatory functions in an organ-like culture model of normal human urothelial cells. Here, we used this model to investigate the involvement of EGF receptor (EGFR) in human urothelial regeneration. Three 4-mm-diameter damaged areas were made in confluent normal human urothelial cell cultures with a biopsy punch. Regeneration was measured, on fixed stained cultures, with an image analyzer, at 4, 24, and 48 hours after injury. Cell proliferation was assessed by 5-bromo-2-deoxyuridine incorporation. To identify EGF family factors potentially involved in the healing process, we studied the effect of these factors on damaged confluent cultures and the level of expression of mRNAs extracted from these cultures. EGFR inhibition of the proliferation and migration of urothelial cells was tested with (1). a specific tyrosine kinase inhibitor (AG1478) and (2). a blocking anti-EGFR antibody (LA22). Exogenously added amphiregulin, EGF, transforming growth factor-alpha and heparin-binding EGF (HB-EGF) stimulated urothelial regeneration. The damaged areas were repaired by regrowth within 48 hours. Both AG1478 and LA22 inhibited the repair (by 50% and 30%, respectively), as well as proliferation and migration. This regeneration was accompanied by increased HB-EGF mRNA expression in cultures of cells from four of six subjects, but no corresponding change in EGFR protein level was observed. These results indicate that the EGFR signaling pathway is involved in urothelial regeneration. Our data support an autocrine role of HB-EGF in this process and suggest that the EGFR pathway is a potential therapeutic target for modulating urothelial cell proliferation. 相似文献