全文获取类型
收费全文 | 11779篇 |
免费 | 690篇 |
国内免费 | 69篇 |
专业分类
耳鼻咽喉 | 65篇 |
儿科学 | 360篇 |
妇产科学 | 249篇 |
基础医学 | 1993篇 |
口腔科学 | 111篇 |
临床医学 | 1119篇 |
内科学 | 2978篇 |
皮肤病学 | 191篇 |
神经病学 | 1030篇 |
特种医学 | 297篇 |
外科学 | 1589篇 |
综合类 | 35篇 |
现状与发展 | 1篇 |
一般理论 | 9篇 |
预防医学 | 714篇 |
眼科学 | 78篇 |
药学 | 741篇 |
中国医学 | 21篇 |
肿瘤学 | 957篇 |
出版年
2023年 | 46篇 |
2022年 | 102篇 |
2021年 | 241篇 |
2020年 | 149篇 |
2019年 | 238篇 |
2018年 | 278篇 |
2017年 | 183篇 |
2016年 | 219篇 |
2015年 | 239篇 |
2014年 | 377篇 |
2013年 | 509篇 |
2012年 | 845篇 |
2011年 | 898篇 |
2010年 | 492篇 |
2009年 | 500篇 |
2008年 | 807篇 |
2007年 | 866篇 |
2006年 | 852篇 |
2005年 | 913篇 |
2004年 | 867篇 |
2003年 | 809篇 |
2002年 | 771篇 |
2001年 | 86篇 |
2000年 | 41篇 |
1999年 | 110篇 |
1998年 | 168篇 |
1997年 | 123篇 |
1996年 | 89篇 |
1995年 | 94篇 |
1994年 | 74篇 |
1993年 | 78篇 |
1992年 | 42篇 |
1991年 | 43篇 |
1990年 | 40篇 |
1989年 | 32篇 |
1988年 | 31篇 |
1987年 | 35篇 |
1986年 | 31篇 |
1985年 | 14篇 |
1984年 | 17篇 |
1983年 | 21篇 |
1982年 | 16篇 |
1981年 | 27篇 |
1980年 | 28篇 |
1979年 | 15篇 |
1978年 | 12篇 |
1977年 | 17篇 |
1976年 | 6篇 |
1970年 | 8篇 |
1968年 | 10篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
81.
Valrie Lang Dominique Mge Monique Semichon Hlne Gary-Gouy Georges Bismuth 《European journal of immunology》1997,27(12):3360-3367
Sam68 has been initially described as a substrate of src kinases during mitosis in fibroblasts. Recent evidence suggests that in T lymphocytes Sam68 may act as an adaptor protein and participate in the early biochemical cascade triggered after CD3 stimulation. A direct interaction between Sam68 and the two src kinases involved in T cell activation, p59fyn and p56lck, as well as a partnership of Sam68 with various key downstream signaling molecules, like phospholipase Cγ-1 and Grb2, has been shown. In this study we analyze the contribution of p56lck, as well as the role of ZAP-70, the second class of protein tyrosine kinase involved in T cell activation, in Sam68 tyrosine phosphorylation in the human Jurkat T cell line. Using the src inhibitor PP1 [4-amino-5-(4-methylphenyl)7-(t-butyl) pyrazolo [3,4-d] pyrymidine] and cell variants with defective expression of p56lck or expressing a dominant negative form of ZAP-70, we demonstrate that, while both p56lck and ZAP-70 are dispensable for the low constitutive phosphorylation of Sam68 observed in Jurkat cells, a cooperation between the two kinases is required to increase its rapid phosphorylation observed in vivo after CD3 stimulation. We also show that recombinant forms of both p56lck and ZAP-70 phosphorylate Sam68 in vitro. However, using CD2 stimulated cells, we observe that p56lck activation by itself does not induce Sam68 tyrosine phosphorylation. We conclude that p59lck and p56lck differently participate in regulating the phosphorylation state of Sam68 in T cells and that ZAP-70 may contribute to Sam68 tyrosine phosphorylation and to the specific recruitment of this molecule after CD3 stimulation. 相似文献
82.
Evaluation of the VITEK 2 System for Rapid Identification of Medically Relevant Gram-Negative Rods 总被引:2,自引:12,他引:2 下载免费PDF全文
Guido Funke Dominique Monnet Chiara deBernardis Alexander von Graevenitz Jean Freney 《Journal of clinical microbiology》1998,36(7):1948-1952
The new VITEK 2 system (bioMérieux) was evaluated at two independent sites with the identification card for gram-negative bacilli (ID-GNB card). Of the 845 strains tested, which represented 70 different taxa belonging to either the family Enterobacteriaceae or the nonenteric bacilli, 716 (84.7%) were correctly identified at the species level. Thirty-two (3.8%) additional strains were identified to the species level after the performance of simple, rapid manual tests (oxidase, hemolysis, indole reaction, motility, and pigmentation). For 80 (9.5%) strains, these additional tests did not lead to an identification at the species level but the correct species identification was given among the organisms listed. Only 7 (0.8%) strains were misidentified, and 10 (1.2%) were not identified. Mistakes were randomly distributed over different taxa. Due to the new, more sensitive fluorescence-based technology of the VITEK 2 system, final results were available after 3 h. Since our evaluation was mainly a stress test, it is predicted that the VITEK 2 system in conjunction with the ID-GNB card would perform well under conditions of a routine clinical laboratory in identifying members of the family Enterobacteriaceae and selected species of nonenteric bacteria. This system is a promising, highly automated new tool for the rapid identification of gram-negative bacilli from human clinical specimens. 相似文献
83.
Baris O Delettre C Amati-Bonneau P Surget MO Charlin JF Catier A Derieux L Guyomard JL Dollfus H Jonveaux P Ayuso C Maumenee I Lorenz B Mohammed S Tourmen Y Bonneau D Malthièry Y Hamel C Reynier P 《Human mutation》2003,21(6):656-656
The OPA1 gene, encoding a dynamin-related GTPase that plays a role in mitochondrial biogenesis, is implicated in most cases of autosomal dominant optic atrophy (ADOA). Sixty-nine pathogenic OPA1 mutations have been reported so far. Most of these are truncating mutations located in the GTPase domain coding region (exons 8-16) and at the 3'-end (exons 27-28). We screened 44 patients with typical ADOA using PCR-sequencing. We also tested 20 sporadic cases of bilateral optic atrophy compatible with ADOA. Of the 18 OPA1 mutations found, 14 have never been previously reported. The novel mutations include one nonsense mutation, 3 missense mutations, 6 deletions, one insertion and 3 exon-skipping mutations. Two of these are de novo mutations, which were found in 2 patients with sporadic optic atrophy. The recurrent c.2708_2711delTTAG mutation was found in 2 patients with a severe congenital presentation of the disease. These results suggest that screening for OPA1 gene mutations may be useful for patients with optic atrophy who have no affected relatives, or when the presentation of the disease is atypical as in the case of early onset optic atrophy. 相似文献
84.
E. Mignot A. Serrano Dominique Laude J. -L. Elghozi J. Dedek B. Scatton 《Journal of neural transmission (Vienna, Austria : 1996)》1985,62(1-2):117-124
Summary The relationship between the concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in the CSF and in the striatum has been evaluated in the rat by measuring the levels of this metabolite in ventricular CSF (by liquid chromatography coupled with electrochemical detection) and in the striatal extracellular fluid (byin vivo voltammetry) after administration of inhibitors of serotonin synthesis or degradation. Pargyline, NSD 1015 and-propyldopacetamide all caused an exponential decline of 5-HIAA in both CSF and striatum. For a given drug, the rate constants for 5-HIAA disappearance were identical in the CSF and in the striatal extracellular fluid. These results confirm the view that CSF 5-HIAA may serve as a good index of brain serotonin turnover. 相似文献
85.
Dominique Bron Dr Pierre Dodion Marcel Rozencweig Alain Delforge Marie-Anne Mattelaer Yvon Kenis Pierre Stryckmans 《Investigational new drugs》1986,4(1):11-16
The effect of 3 anthracene derivatives, mitoxantrone, ametantrone, bisantrene, on 4 normal human bone marrows, was studied using the myeloid stem cell assay developed by Pike and Robinson, in order to define to what extent this test could be used to predict the relative clinical hematologic toxicity of new anticancer agents. For the 3 drugs, an exponential relationship between colony survival and drug concentration was found, but was much steeper for mitoxantrone (slope = -195.2 ± 8.8/g/ml) than for ametantrone (slope = 5.1 ± 1.0/g/ml, p0.001) and bisantrene (slope = 7.1 ± 0.3/g/ml, p0.001). The difference of slope between ametantrone and bisantrene was of borderline significance (p0.05). The ratios of concentrations inducing a 50% growth inhibition for mitoxantrone versus bisantrene and for ametantrone versus bisantrene were close to the corresponding ratios of concentrations inducing a 90% growth inhibition. The relative in vitro toxicities reproduce very well the relative myelosuppression observed in clinical trials with mitoxantrone versus bisantrene but the results were less satisfactory for the comparison of these 2 agents with ametantrone. In addition, our data suggest that, for these 3 compounds, intrinsic myeloid progenitor sensitivity is a major determinant of leukopenia. 相似文献
86.
Fatima Sheikh Nicole Brandt Dominique Vinh Rebecca D. Elon 《Journal of the American Medical Directors Association》2021,22(6):1199-1205
Despite the dynamic demands in the nursing home (NH), a definitive approach to managing chronic pain in older adults has yet to be established. Due to concerns for potential adverse pharmacologic effects, balancing appropriate pain management is a challenge among NH residents. The challenges encompass but are not limited to medical complexities, functional disabilities, and physical frailty. Barriers to the successful implementation of a comprehensive chronic pain management at the NH may include ambiguous directions on specific therapeutic interventions, insufficient guidance on treatment duration, and limited available treatment options. The Centers for Medicare and Medicaid Services’ reporting requirement of adequate pain control among NH residents coupled with widely variable clinician-prescribing habits highlights the difficulties in overcoming the preceding challenges and barriers. The Coronavirus Disease 2019 (COVID-19) pandemic has further complicated pain management due to its negative consequences on well-being of residents of NHs. Associated symptoms of psychosocial stress, anxiety and depression, and chronic pain symptoms can exacerbate during the COVID-19 pandemic, leading to increased requirement for pain medications including but not limited to opioids.Pain is a multidimensional symptom and requires a strategic multimodal approach for its management. Nonpharmacologic modalities are underutilized in the NH setting and are the preferred first steps for mild pain, and nonopioid pharmacological agents can be added as a second step for a synergistic effect for moderate to severe pain. Opioids should be used as a last resort. Short-acting opioids are preferred over extended-release/long-acting opioids for chronic pain. Clinicians are encouraged to engage residents in proactive strategies in managing their pain, and to set realistic expectations toward improving their quality of life, as complete elimination of pain is not feasible in most cases.This review article provides the interdisciplinary team with a contemporary perspective of the multitude of changes and challenges influencing the prescribing as well as deprescribing of various pain medications. 相似文献
87.
Anne Sophie Kruit Kaj Brouwers Dominique van Midden Her Zegers Erik Koers Nens van Alfen Stefan Hummelink Dietmar J. O. Ulrich 《Transplant international》2021,34(2):365-375
The current standard for composite tissue preservation is static cold storage (SCS) and is limited to 6 h until irreversible muscle damage occurs. Extracorporeal perfusion (ECP) is a promising technique for prolonged preservation, however, functional results have been scarcely researched. This article assessed neuromuscular function and compared results to histological alterations to predict muscle damage after ECP. Forelimbs of twelve Dutch landrace pigs were amputated and preserved by 4 h SCS at 4–6 °C (n = 6) or 18 h mid-thermic ECP with University of Wisconsin solution (n = 6). Limbs were replanted and observed for 12 h. Sham surgery was performed on contralateral forelimbs (n = 12). Histology analysis scored four subgroups representing different alterations (higher score equals more damage). Muscle contraction after median nerve stimulation was comparable between ECP, SCS, and sham limbs (P = 0.193). Histology scores were higher in ECP limbs compared to SCS limbs (4.8 vs. 1.5, P = 0.013). This was mainly based on more oedema in these limbs. In-vivo muscle contraction was well preserved after 18 h ECP compared to short SCS, although histology seemed inferior in this group. Histology, therefore, did not correlate to muscle function at 12 h after replantation. This leads to the question whether histology or neuromuscular function is the best predictor for transplant success. 相似文献
88.
High Cardiovascular Risk in Older Men with Poor Bone Microarchitecture—The Prospective STRAMBO Study
Pawel Szulc Dominique Foesser Roland Chapurlat 《Journal of bone and mineral research》2021,36(5):879-891
Data on the association between bone microarchitecture and cardiovascular disease (CVD) in men are scarce. We studied the link of bone microarchitecture and areal bone mineral density (aBMD) with the risk of major adverse coronary event (MACE) in a cohort of men aged 60 to 87 years followed prospectively for 8 years. At baseline, aBMD was measured using a Hologic Discovery-A device. Bone microarchitecture was assessed at distal radius and tibia by high-resolution peripheral quantitative computed tomography (XtremeCT Scanco device). During the study, 53 men had incident MACE. The analyses were adjusted for confounders related to bone and CVD. In 813 men (53 MACEs), higher aBMD at the lumbar spine, hip, whole body, and radius was associated with lower risk of MACE (hazard ratio [HR] = 0.44–0.71/SD, p < .025 to < .001). In 745 men having valid distal radius scan (47 MACEs), higher cortical density (Ct.BMD) and higher cortical thickness (Ct.Thd) were associated with lower risk of MACE. This risk was higher in men in the lowest quintile of cortical measures versus the four upper quintiles combined (Ct.BMD: HR = 2.12, 95% confidence interval [CI] 1.08–4.17, p < .025). Findings were similar in 779 men having valid distal tibia scan (48 MACEs). At both sites, higher estimated stiffness and higher failure load were associated with a lower risk of MACE. The risk of MACE was higher in men in the lowest quintile of the measures of bone strength versus four upper quintiles jointly (distal radius stiffness: HR = 2.46, 95% CI 1.27–4.74, p < .01). Similar results were obtained in 638 men without prior fragility fracture and in 689 men without ischemic heart disease at baseline. Thus, in older men followed prospectively for 8 years, higher aBMD, preserved cortical bone status, and higher estimated bone strength were associated with lower risk of MACE after adjustment for relevant confounders. © 2021 American Society for Bone and Mineral Research (ASBMR). 相似文献
89.
90.
Functional expression of 4-1BB (CD137) in the inflammatory tissue in Crohn's disease 总被引:2,自引:0,他引:2
Maerten P Geboes K De Hertogh G Shen C Cadot P Bullens DM Van Assche G Penninckx F Rutgeerts P Ceuppens JL 《Clinical immunology (Orlando, Fla.)》2004,112(3):239-246
4-1BB ligand (L) expressed on antigen presenting cells (APC) interacts with 4-1BB, expressed on activated T cells and this interaction costimulates T cells to secrete cytokines and to proliferate. We investigated whether 4-1BB/4-1BBL interactions might be involved in the pathogenesis of Crohn's disease (CD). In immunohistochemistry, we found 4-1BB expression on lamina propria (LP) cells in inflamed and to a lesser extend in non-inflamed gut tissue from CD patients. mRNA levels for 4-1BB were also elevated in intestinal CD tissue. In contrast, only few 4-1BB-expressing cells were found in inflamed tissue from ulcerative colitis (UC) patients and almost no positive cells were found in control intestinal tissue. 4-1BB expression was better sustained on in vitro activated lamina propria T cells from CD patients compared to controls. Finally, agonistic anti-4-1BB antibody enhanced interferon-gamma (IFN-gamma) production and proliferation of lamina propria T cells from CD patients. Taken together, our data suggest that 4-1BB/4-1BBL interactions contribute to the persistence of gut inflammation in CD. 相似文献