全文获取类型
收费全文 | 8436篇 |
免费 | 536篇 |
国内免费 | 58篇 |
专业分类
耳鼻咽喉 | 42篇 |
儿科学 | 201篇 |
妇产科学 | 225篇 |
基础医学 | 1315篇 |
口腔科学 | 51篇 |
临床医学 | 805篇 |
内科学 | 2029篇 |
皮肤病学 | 145篇 |
神经病学 | 811篇 |
特种医学 | 249篇 |
外科学 | 1490篇 |
综合类 | 40篇 |
一般理论 | 3篇 |
预防医学 | 528篇 |
眼科学 | 92篇 |
药学 | 453篇 |
中国医学 | 10篇 |
肿瘤学 | 541篇 |
出版年
2023年 | 45篇 |
2022年 | 80篇 |
2021年 | 174篇 |
2020年 | 111篇 |
2019年 | 168篇 |
2018年 | 213篇 |
2017年 | 152篇 |
2016年 | 152篇 |
2015年 | 199篇 |
2014年 | 293篇 |
2013年 | 399篇 |
2012年 | 586篇 |
2011年 | 600篇 |
2010年 | 385篇 |
2009年 | 341篇 |
2008年 | 548篇 |
2007年 | 578篇 |
2006年 | 574篇 |
2005年 | 548篇 |
2004年 | 581篇 |
2003年 | 557篇 |
2002年 | 582篇 |
2001年 | 46篇 |
2000年 | 62篇 |
1999年 | 74篇 |
1998年 | 124篇 |
1997年 | 97篇 |
1996年 | 88篇 |
1995年 | 75篇 |
1994年 | 67篇 |
1993年 | 56篇 |
1992年 | 45篇 |
1991年 | 28篇 |
1990年 | 28篇 |
1989年 | 32篇 |
1988年 | 21篇 |
1987年 | 31篇 |
1986年 | 28篇 |
1985年 | 22篇 |
1984年 | 29篇 |
1983年 | 22篇 |
1982年 | 31篇 |
1981年 | 32篇 |
1980年 | 15篇 |
1979年 | 12篇 |
1978年 | 13篇 |
1977年 | 10篇 |
1976年 | 11篇 |
1975年 | 8篇 |
1974年 | 9篇 |
排序方式: 共有9030条查询结果,搜索用时 11 毫秒
81.
Pascal Sève Sylvie Isaac Olivier Trédan Pierre-Jean Souquet Yves Pachéco Maurice Pérol Laurence Lafanéchère Aurélie Penet Eva-Laure Peiller Charles Dumontet 《Clinical cancer research》2005,11(15):5481-5486
PURPOSE: To determine the prevalence and the prognostic value of microtubule component expression in tumors of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Expression of microtubular components was immunohistochemically examined in 93 tumor samples from untreated patients with stage III and IV NSCLC. All patients received vinorelbine-based chemotherapy. Response to chemotherapy, progression-free survival, and overall survival were correlated with the expression of microtubule proteins. RESULTS: The response rate was 27.3% (21 partial responses among 77 valuable patients). Although expression of microtubule components was not associated with the response rate, high class III beta-tubulin expression was correlated with resistance to vinorelbine, defined as disease progression under treatment. Patients whose tumors expressed high levels of class III beta-tubulin isotype had shorter progression-free survival and overall survival (P = 0.002 and 0.001, respectively). High Delta2 alpha-tubulin expression was associated with a shorter overall survival (P = 0.018). Tubulin II levels were not found to be correlated with patient outcome. A multivariate analysis, taking into account sex, age, histology, stage, weight loss, and class II beta-tubulin, class III beta-tubulin, and Delta2 alpha-tubulin levels, confirmed that class III beta-tubulin expression was independently correlated with progression-free survival (P = 0.04) and overall survival (P = 0.012). CONCLUSIONS: These findings suggest that a high level of expression of class III beta-tubulin in tumor cells is associated with resistance to vinorelbine and a poor prognosis in patients with NSCLC receiving vinorelbine-based chemotherapy. 相似文献
82.
Christopher G Willett Yves Boucher Dan G Duda Emmanuelle di Tomaso Lance L Munn Ricky T Tong Sergey V Kozin Lucine Petit Rakesh K Jain Daniel C Chung Dushyant V Sahani Sanjeeva P Kalva Kenneth S Cohen David T Scadden Alan J Fischman Jeffrey W Clark David P Ryan Andrew X Zhu Lawrence S Blaszkowsky Paul C Shellito Mari Mino-Kenudson Gregory Y Lauwers 《Journal of clinical oncology》2005,23(31):8136-8139
83.
84.
Tim Du Kelly B. Choi Anada Silva George R. Golding Linda Pelude Romeo Hizon Ghada N. Al-Rawahi James Brooks Blanda Chow Jun C. Collet Jeannette L. Comeau Ian Davis Gerald A. Evans Charles Frenette Guanghong Han Jennie Johnstone Pamela Kibsey Kevin C. Katz Joanne M. Langley Bonita E. Lee Yves Longtin Dominik Mertz Jessica Minion Michelle Science Jocelyn A. Srigley Paula Stagg Kathryn N. Suh Nisha Thampi Alice Wong Susy S. Hota 《Emerging infectious diseases》2022,28(6):1128
We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult patients in Canadian Nosocomial Infection Surveillance Program hospitals during 2015–2019. The study encompassed 18,455 CDI cases, 13,735 (74.4%) HA and 4,720 (25.6%) CA. During 2015–2019, HA CDI rates decreased by 23.8%, whereas CA decreased by 18.8%. HA CDI was significantly associated with increased 30-day all-cause mortality as compared with CA CDI (p<0.01). Of 2,506 isolates analyzed, the most common ribotypes (RTs) were RT027, RT106, RT014, and RT020. RT027 was more often associated with CDI-attributable death than was non-RT027, regardless of acquisition type. Overall resistance C. difficile rates were similar for all drugs tested except moxifloxacin. Adult HA and CA CDI rates have declined, coinciding with changes in prevalence of RT027 and RT106. Infection prevention and control and continued national surveillance are integral to clarifying CDI epidemiology, investigation, and control. 相似文献
85.
Yves Chaput Claude de Montigny Pierre Blier 《Naunyn-Schmiedeberg's archives of pharmacology》1986,333(4):342-348
Summary Citalopram (CIT), is a selective serotonin (5-HT) reuptake blocker and a clinically effective antidepressant. The present electrophysiological studies were undertaken to investigate in vivo the acute and long-term effects of CIT administration on 5-HT neurotransmission. In a first series of experiments, a single dose of CIT (0.05–0.5 mg/kg) was administered intravenously to naive rats while recording the activity of a 5-HT-containing neuron in the nucleus raphe dorsalis. A dose-response relationship of the inhibitory effect of CIT on the firing activity of 5-HT neurons was obtained with an ED50 of 0.23±0.03 mg/kg. In a second series of experiments, rats were treated with CIT (20 mg/kg/day, i.p.) for 2, 7 and 14 days. In rats treated for 2 days, there was a marked reduction in the firing activity of 5-HT neurons in the nucleus raphe dorsalis; there was a partial recovery after 7 days and a complete recovery after 14 days of treatment. The response of 5-HT neurons to intravenously administered LSD was decreased in rats treated for 14 days with CIT, indicating a desensitization of the somatodendritic 5-HT autoreceptor. In a third series of experiments, carried out in rats treated with CIT (20 mg/kg/day, i.p.) for 14 days, the suppression of firing activity of CA3 hippocampal pyramidal neurons produced by microiontophoretically-applied 5-HT and by the electrical activation of the ascending 5-HT pathway was measured. Long-term treatment with CIT did not modify the responsiveness of these neurons to microiontophoretically-applied 5-HT; however, the effect of the electrical activation of the ascending 5-HT pathway on these same neurons was enhanced. To determine if 5-HT reuptake blockade could be responsible for this enhancement, CIT (1 mg/kg) was injected intravenously in naive rats while stimulating the ascending 5-HT pathway; it failed to modify the effectiveness of the stimulation. To assess the involvement of the 5-HT terminal autoreceptor, methiothepin, a 5-HT autoreceptor antagonist, was injected intravenously (1 mg/kg) in naive rats and in rats treated for 14 days with CIT while stimulating the ascending 5-HT pathway. Methiothepin enhanced the effect of the stimulation in naive rats but failed to do so in the CIT-treated rats. It is concluded that long-term CIT treatment enhances 5-HT neurotransmission by desensitizing both the somatodendritic and terminal 5-HT autoreceptors. 相似文献
86.
Horsmans Y Hu K Ruffin M Wang Y Song D Bouillaud E Wang Y Mazur D Botha FP Heuman DM 《Journal of clinical pharmacology》2012,52(4):552-558
Pasireotide is a novel, multireceptor-targeted somatostatin analogue with high affinity for sst(1,2,3) and sst(5) under clinical evaluation in tumors of neuroendocrine origin, including Cushing's disease, acromegaly, and neuroendocrine tumors. In this phase I, open-label, multicenter study, the pharmacokinetics and safety of a single subcutaneous (SC) injection of pasireotide 600 μg were evaluated in adults with normal hepatic function (n = 15) and mild (n = 6), moderate (n = 7), or severe hepatic impairment (n = 6). Following a single dose of pasireotide SC 600 μg, there were no significant differences in the plasma exposure of pasireotide between participants with normal hepatic function or mild hepatic impairment. Subjects with moderate and severe hepatic impairment showed an increase in AUC(∞) by 56% and 42%, respectively; this increase was 60% and 79% respectively, after adjusting for differences in age, BMI, and baseline serum albumin level between treatment groups. The incidence and severity of adverse events were similar across cohorts, with no clinically relevant differences in type or frequency of adverse events between cohorts. In conclusion, a single dose of pasireotide SC 600 μg was well tolerated in subjects with hepatic impairment. Drug exposure in subjects with mild hepatic impairment was similar to that seen in healthy volunteers, whereas subjects with moderate and severe hepatic impairment experienced higher exposure to pasireotide. Adjustment of the pasireotide dose may be required for patients with moderate and severe hepatic impairment. 相似文献
87.
Sanchez C Mathy-Hartert M Deberg MA Ficheux H Reginster JY Henrotin YE 《Biochemical pharmacology》2003,65(3):377-388
This study was designed to investigate the effects of rhein, the active metabolite of diacerhein, on the metabolic functions of human chondrocytes cultured in alginate beads.Enzymatically isolated osteoarthritic (OA) chondrocytes were cultured in alginate beads in a well-defined culture medium for 12 days. Rhein was tested in a range of concentrations comprised between 10(-7) and 4 x 10(-5)M, in the presence or absence of 10(-10)M IL-1beta. Interleukin (IL)-6 and -8, macrophage inflammatory protein (MIP-1beta), stromelysin-1 (MMP-3), aggrecan (AGG), tissue inhibitor of metalloproteinases-1 (TIMP-1), prostaglandin E(2) (PGE(2)) and nitric oxide (NO) productions were assayed. Cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) mRNA steady-state levels were also quantified. In the basal condition, 10(-5)M rhein increased by 46.5% the production of AGG, decreased by 17-30% the production of IL-6, MMP-3, NO and MIP-1beta but enhanced by 50% the production of PGE(2). IL-1beta increased IL-6, IL-8, MIP-1beta, NO, PGE(2) and MMP-3 productions, but inhibited AGG and TIMP-1 synthesis. Rhein partially reversed the effect of IL-1beta on TIMP-1 and NO production, had no effect on AGG, IL-6 and MIP-1beta production, but up-regulated the IL-1beta stimulated PGE(2) production. The COX-2 and iNOS mRNA levels and IL-8 production were not modified by rhein.Overall, these results contribute to explain the clinical efficiency of rhein and give new information on its mechanisms of action. 相似文献
88.
Garnier Y Kadyrov M Gantert M Einig A Rath W Huppertz B 《European journal of obstetrics, gynecology, and reproductive biology》2008,140(2):152-157
OBJECTIVES: Antenatal infections are associated with an increased risk of perinatal morbidity and mortality. Systemic application of endotoxins to the fetus results in an increase in placental vascular resistance and chronic reduction in umbilical blood flow. We studied morphological alterations of the placenta in response to fetal inflammation in the preterm sheep. STUDY DESIGN: Therefore, 14 fetal sheep were chronically instrumented at a mean gestational age of 107+/-1 days (term is 147 days). Four days after surgery fetuses received 100 ng lipopolysaccharide (LPS; n=8) or saline (control; n=6) intravenously. Fetal heart rate and arterial blood pressure were monitored continuously while blood gases and acid-base balance were measured at time points 0, +1, +3, +6, +12, +24, +48 and +72 h. Three days after LPS application placental cotyledons were analyzed by immunohistochemistry and morphometry. Different primary antibodies like AE 1 and AE 3 against cytokeratins were used. Secondary antibodies were visualized with 3-amino-9-ethylcarbazole (AEC) or using the Vectastain kit (Vector Laboratories, Burlingame, CA). Double staining was carried out first by utilizing Vectastain kit (black), followed by AEC staining (red). Counterstaining was performed with haematoxylin. RESULTS: Fetal tachycardia and hypertension were induced transiently during the first 12h after LPS application. Fetuses suffered from mild hypoxaemia while acidemia was absent. Morphometry revealed a non-significant shift in the relation of maternal and fetal placental compartments towards the maternal parts in response to LPS treatment. Endotoxin induced an increased proliferation in both compartments of the placenta with a 3.2-fold increase on the maternal and a 1.8-fold increase on the fetal side. CONCLUSIONS: Systemic endotoxin exposure of the preterm fetal sheep leads to a change in the gross organization of the placenta and changes in the proliferation patterns in both placental compartments. These rearrangements inside the placenta may disturb its organ function and subsequently lead to fetal morbidity associated with the fetal inflammatory response syndrome and chronic placental dysfunction, respectively. 相似文献
89.
90.
Senat MV Bussières L Couderc S Roume J Rozenberg P Bouyer J Ville Y 《American journal of obstetrics and gynecology》2007,196(1):53-53.e6