全文获取类型
收费全文 | 2405篇 |
免费 | 150篇 |
国内免费 | 10篇 |
专业分类
耳鼻咽喉 | 7篇 |
儿科学 | 35篇 |
妇产科学 | 30篇 |
基础医学 | 341篇 |
口腔科学 | 80篇 |
临床医学 | 183篇 |
内科学 | 712篇 |
皮肤病学 | 51篇 |
神经病学 | 184篇 |
特种医学 | 93篇 |
外科学 | 352篇 |
综合类 | 15篇 |
预防医学 | 60篇 |
眼科学 | 11篇 |
药学 | 207篇 |
中国医学 | 15篇 |
肿瘤学 | 189篇 |
出版年
2023年 | 13篇 |
2022年 | 42篇 |
2021年 | 68篇 |
2020年 | 56篇 |
2019年 | 58篇 |
2018年 | 70篇 |
2017年 | 41篇 |
2016年 | 41篇 |
2015年 | 45篇 |
2014年 | 74篇 |
2013年 | 78篇 |
2012年 | 123篇 |
2011年 | 125篇 |
2010年 | 60篇 |
2009年 | 48篇 |
2008年 | 108篇 |
2007年 | 83篇 |
2006年 | 102篇 |
2005年 | 118篇 |
2004年 | 105篇 |
2003年 | 84篇 |
2002年 | 86篇 |
2001年 | 53篇 |
2000年 | 83篇 |
1999年 | 67篇 |
1998年 | 37篇 |
1997年 | 30篇 |
1996年 | 24篇 |
1995年 | 22篇 |
1994年 | 19篇 |
1993年 | 21篇 |
1992年 | 60篇 |
1991年 | 49篇 |
1990年 | 53篇 |
1989年 | 47篇 |
1988年 | 35篇 |
1987年 | 42篇 |
1986年 | 35篇 |
1985年 | 41篇 |
1984年 | 27篇 |
1983年 | 19篇 |
1982年 | 11篇 |
1979年 | 19篇 |
1978年 | 17篇 |
1977年 | 13篇 |
1974年 | 8篇 |
1973年 | 14篇 |
1971年 | 16篇 |
1970年 | 19篇 |
1969年 | 7篇 |
排序方式: 共有2565条查询结果,搜索用时 31 毫秒
991.
992.
Rose NR Woon EC Tumber A Walport LJ Chowdhury R Li XS King ON Lejeune C Ng SS Krojer T Chan MC Rydzik AM Hopkinson RJ Che KH Daniel M Strain-Damerell C Gileadi C Kochan G Leung IK Dunford J Yeoh KK Ratcliffe PJ Burgess-Brown N von Delft F Muller S Marsden B Brennan PE McDonough MA Oppermann U Klose RJ Schofield CJ Kawamura A 《Journal of medicinal chemistry》2012,55(14):6639-6643
The JmjC oxygenases catalyze the N-demethylation of N(ε)-methyl lysine residues in histones and are current therapeutic targets. A set of human 2-oxoglutarate analogues were screened using a unified assay platform for JmjC demethylases and related oxygenases. Results led to the finding that daminozide (N-(dimethylamino)succinamic acid, 160 Da), a plant growth regulator, selectively inhibits the KDM2/7 JmjC subfamily. Kinetic and crystallographic studies reveal that daminozide chelates the active site metal via its hydrazide carbonyl and dimethylamino groups. 相似文献
993.
Ogawa B Wang L Ohishi T Taniai E Akane H Suzuki K Mitsumori K Shibutani M 《Archives of toxicology》2012,86(5):779-790
We have recently shown that maternal exposure to acrylamide (AA) impaired neurogenesis in rat offspring measured by the increase
in interneurons producing reelin, a molecule regulating migration and correct positioning of developing neurons, in the hippocampal
dentate gyrus. To clarify the cellular target of AA on hippocampal neurogenesis and its reversibility after maternal exposure,
pregnant Sprague–Dawley rats were given drinking water containing AA at 0, 4, 20, 100 ppm on day 10 of pregnancy through day
21 after delivery on weaning. Male offspring were examined immunohistochemically on postnatal day (PND) 21 and PND 77. For
comparison, male pups of direct AA-injection control during lactation (50 mg/kg body weight, intraperitoneally, 3 times/week)
were also examined. On PND 21, maternal AA-exposure decreased progenitor cell proliferation in the subgranular zone (SGZ)
from 20 ppm accompanied with increased density of reelin-producing interneurons and NeuN-expressing mature neurons within
the hilus at 100 ppm, similar to the direct AA-injection control. In the SGZ examined at 100 ppm, cellular populations immunoexpressing
doublecortin or dihydropyrimidinase-like 3, suggesting postmitotic immature granule cells, were decreased. On PND 77, the
SGZ cell proliferation and reelin-producing interneuron density recovered, while the hilar mature neurons sustained to increase
from 20 ppm, similar to the direct AA-injection control. Thus, developmental exposure to AA reversibly affects hippocampal
neurogenesis targeting the proliferation of type-3 progenitor cells resulting in a decrease in immature granule cells in rats.
A sustained increase in hilar mature neurons could be the signature of the developmental effect of AA. 相似文献
994.
Ohishi T Wang L Akane H Shiraki A Goto K Ikarashi Y Suzuki K Mitsumori K Shibutani M 《Reproductive toxicology (Elmsford, N.Y.)》2012,34(3):408-419
To examine the effects of developmental manganese (Mn)-exposure on hippocampal neurogenesis, pregnant rats were treated with MnCl(2)·4H(2)O in the diet at 32, 160 or 800ppm from gestation day 10 to day 21 after delivery. Serum concentrations of thyroid-related hormones were examined in offspring exposed to MnCl(2)·4H(2)O at 800 or 1600ppm. Immunohistochemical analysis revealed increased doublecortin-positive cells in the subgranular zone of the dentate gyrus on postnatal day (PND) 21 following exposure to MnCl(2)·4H(2)O at 800ppm, indicating an increase of type-3 progenitor or immature granule cells. Reelin-positive cells, suggestive of γ-aminobutyric acid-ergic interneurons in the dentate hilus, also increased at 800ppm on PND 21. Brain Mn concentrations increased in offspring on PND 21 at 160 and 800ppm, whereas brain concentrations in the dams were unchanged. Serum concentrations of triiodothyronine and thyroxine decreased at 800 and 1600ppm, whereas thyroid-stimulating hormone increased only after exposure at 800ppm. All changes disappeared on PND 77. Thus, maternal exposure to MnCl(2)·4H(2)O at 800ppm mildly and reversibly affects neurogenesis targeting late-stage differentiation in the hippocampal dentate gyrus of rat offspring. Direct effects of accumulated Mn in the developing brain might be implicated in the mechanism of the development of aberrations in neurogenesis; however, indirect effects through thyroid hormone fluctuations might be rather minor. 相似文献
995.
996.
997.
In this study, we examined the effect of SUN N8075, a radical scavenger with neuroprotective properties, on murine retinal damage induced by intravitreous injection of N-methyl-d-aspartate (NMDA) or high-intraocular pressure (IOP). In both models, systemic administration of SUN N8075 decreased the cell loss in the ganglion cell layer (GCL) after retinal damage occurred. Moreover, SUN N8075 reduced the number of apoptotic cells and the expression of an oxidative stress marker in GCL in the NMDA model. These findings suggest that SUN N8075 has a neuroprotective effect against retinal damage, presumably via the radical scavenging effect. 相似文献
998.
Fumiko Sekiguchi Yuka Aoki Maiko Nakagawa Daiki Kanaoka Yuta Nishimoto Maho Tsubota-Matsunami Rumi Yamanaka Shigeru Yoshida Atsufumi Kawabata 《British journal of pharmacology》2013,168(3):734-745
Background and Purpose
The Cav3.2 isoform of T-type Ca2+ channels (T channels) is sensitized by hydrogen sulfide, a pro-nociceptive gasotransmitter, and also by PKA that mediates PGE2-induced hyperalgesia. Here we examined and analysed Cav3.2 sensitization via the PGE2/cAMP pathway in NG108-15 cells that express Cav3.2 and produce cAMP in response to PGE2, and its impact on mechanical nociceptive processing in rats.Experimental Approach
In NG108-15 cells and rat dorsal root ganglion (DRG) neurons, T-channel-dependent currents (T currents) were measured with the whole-cell patch-clamp technique. The molecular interaction of Cav3.2 with A-kinase anchoring protein 150 (AKAP150) and its phosphorylation were analysed by immunoprecipitation/immunoblotting in NG108-15 cells. Mechanical nociceptive threshold was determined by the paw pressure test in rats.Key Results
In NG108-15 cells and/or rat DRG neurons, dibutyryl cAMP (db-cAMP) or PGE2 increased T currents, an effect blocked by AKAP St-Ht31 inhibitor peptide (AKAPI) or KT5720, a PKA inhibitor. The effect of PGE2 was abolished by RQ-00015986-00, an EP4 receptor antagonist. AKAP150 was co-immunoprecipitated with Cav3.2, regardless of stimulation with db-cAMP, and Cav3.2 was phosphorylated by db-cAMP or PGE2. In rats, intraplantar (i.pl.) administration of db-cAMP or PGE2 caused mechanical hyperalgesia, an effect suppressed by AKAPI, two distinct T-channel blockers, NNC 55-0396 and ethosuximide, or ZnCl2, known to inhibit Cav3.2 among T channels. Oral administration of RQ-00015986-00 suppressed the PGE2-induced mechanical hyperalgesia.Conclusion and Implications
Our findings suggest that PGE2 causes AKAP-dependent phosphorylation and sensitization of Cav3.2 through the EP4 receptor/cAMP/PKA pathway, leading to mechanical hyperalgesia in rats. 相似文献999.
Yamamoto K Hayakawa Y Kousuge Y Wakoh M Sekiguchi H Yakushiji M Farman AG 《Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics》2003,95(1):109-118
OBJECTIVE: This clinical study compares the diagnostic value of interactive 3-dimensional tuned-aperture computed tomography (TACT) with conventional dentoalveolar radiographic examinations of impacted maxillary incisors. STUDY DESIGN: TACT was compared variously with conventional intraoral, occlusal, rotational panoramic, and lateral cephalographic examinations. Sixteen dentists independently evaluated the clarity of anatomic structures of impacted anterior maxillary teeth and surrounding tissues. Estimation of confidence in clinical assessment of the patient was made together with a determination of the diagnostic potential of the studied modalities for altering treatment plans. RESULTS: TACT was found to significantly improve depiction of the buccal/palatal position of the impacted tooth and its relationship with adjacent teeth (P < .0001) irrespective of the availability of lateral cephalograms. Subjective assessments for clinical decision making approximated a 10% increase in confidence ratings with TACT. The added diagnostic value with TACT varied from case to case. CONCLUSIONS: The interactive 3-dimensional TACT display was perceived to be more informative for assessing impacted teeth and their relation to surrounding tissues than conventional methods in some cases but not in others. TACT altered treatment-option selection in some instances. 相似文献
1000.
Seiji Niho Kaoru Kubota Keiji Nihei Ikuo Sekine Minako Sumi Risa Sekiguchi Jumpei Funai Sotaro Enatsu Yuichiro Ohe Tomohide Tamura 《Clinical lung cancer》2013,14(1):62-69
BackgroundPemetrexed has radiosensitizing potential when evaluated in vitro in combination with platinum-containing compounds and radiation. We determined the recommended dose (RD) of thoracic radiotherapy (TRT) with a concurrent chemotherapy combination of pemetrexed and cisplatin in Japanese patients with nonsquamous non–small-cell lung cancer (NSCLC).Patients and MethodsEligible patients were histologically confirmed as having locally advanced nonsquamous NSCLC. Study treatment consisted of 2 phases: concurrent chemoradiation and consolidation. In the concurrent chemoradiation phase, all patients received pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 on day 1 of a 21-day interval for 3 cycles. The first 6 patients were given 60 Gy concurrently at level 1 dose (L1D). If dose-limiting toxicity (DLT) occurred in < 2 patients at L1D, radiation was escalated to 66 Gy (level 2 dose [L2D]).ResultsEighteen patients were treated and completed chemoradiotherapy; 12 completed the consolidation phase. In the concurrent chemoradiation phase, 1 patient experienced 2 DLTs [grade 3 anorexia and diarrhea] at L1D. Because no DLT was observed at L2D, it was determined to be the RD. Common toxicities ≥grade 3 were neutropenia and leukopenia. At L1D, 1 patient each experienced grade 2 and grade 3 pneumonitis, and 2 patients experienced grade 2 esophagitis. Six patients experienced grade 2 pneumonitis and 3 patients experienced grade 2 esophagitis at L2D. Fifteen patients achieved partial response (PR), 2 had stable disease (SD), and 1 had progressive disease (PD).ConclusionExpected toxicities from concurrent chemoradiation were not worsened with concurrent TRT at a total dose of 66 Gy combined with pemetrexed in Japanese patients with locally advanced (LA) nonsquamous NSCLC. 相似文献