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151.
Vanessa Kaplum Juliana Cogo Diego Pereira Sangi Tania Ueda-Nakamura Arlene Gon?alves Corrêa Celso Vataru Nakamura 《Antimicrobial agents and chemotherapy》2016,60(6):3433-3444
Leishmaniasis is endemic in 98 countries and territories worldwide. The therapies available for leishmaniasis have serious side effects, thus prompting the search for new therapies. The present study investigated the antileishmanial activities of 2,3-diarylsubstituted quinoxaline derivatives against Leishmania amazonensis. The antiproliferative activities of 6,7-dichloro-2,3-diphenylquinoxaline (LSPN329) and 2,3-di-(4-methoxyphenyl)-quinoxaline (LSPN331) against promastigotes and intracellular amastigotes were assessed, and the cytotoxicities of LSPN329 and LSPN331 were determined. Morphological and ultrastructural alterations were examined by electron microscopy, and biochemical alterations, reflected by the mitochondrial membrane potential (ΔΨm), mitochondrial superoxide anion (O2·−) concentration, the intracellular ATP concentration, cell volume, the level of phosphatidylserine exposure on the cell membrane, cell membrane integrity, and lipid inclusions, were evaluated. In vivo antileishmanial activity was evaluated in a murine cutaneous leishmaniasis model. Compounds LSPN329 and LSPN331 showed significant selectivity for promastigotes and intracellular amastigotes and low cytotoxicity. In promastigotes, ultrastructural alterations were observed, including an increase in lipid inclusions, concentric membranes, and intense mitochondrial swelling, which were associated with hyperpolarization of ΔΨm, an increase in the O2·− concentration, decreased intracellular ATP levels, and a decrease in cell volume. Phosphatidylserine exposure and DNA fragmentation were not observed. The cellular membrane remained intact after treatment. Thus, the multifactorial response that was responsible for the cellular collapse of promastigotes was based on intense mitochondrial alterations. BALB/c mice treated with LSPN329 or LSPN331 showed a significant decrease in lesion thickness in the infected footpad. Therefore, the antileishmanial activity and mitochondrial mechanism of action of LSPN329 and LSPN331 and the decrease in lesion thickness in vivo brought about by LSPN329 and LSPN331 make them potential candidates for new drug development for the treatment of leishmaniasis. 相似文献
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154.
Parellada M Moreno C Moreno M Espliego A de Portugal E Arango C 《European neuropsychopharmacology》2012,22(11):787-799
Much literature has been written in the field of child psychiatry regarding the placebo as a tool to test drug efficacy in clinical trials, but quite little regarding the placebo effect itself or its clinical use in child psychiatry. In this article, we aim to critically review the literature regarding the placebo effect in children and adolescents with mental disorders, focusing especially on factors influencing the placebo effect and how they may influence the interpretation of clinical trials. The placebo effect seems to be more marked in children than adults, and particularly in children and adolescents with depression, although it is pervasive across ages and is present in non-psychiatric conditions as well. The use of a placebo in clinical trials as a comparator with drugs that have moderate efficacy at most makes it difficult to obtain positive results, and much effort is needed to design very high quality clinical trials that may overcome the limitations of using a placebo. In addition, the placebo effect across ages and clinical conditions must be tested directly (compared with no treatment whenever possible), in order to characterise which placebos work for what and to determine their use in clinical settings. 相似文献
155.
Giordani RB Junior CO de Andrade JP Bastida J Zuanazzi JA Tasca T de Almeida MV 《Chemical biology & drug design》2012,80(1):129-133
Six lycorine derivatives were prepared, characterized, and evaluated for their in vitro anti‐Trichomonas vaginalis activity. Compounds bearing an acetyl ( 2 ), lauroyl ( 3 ), benzoyl ( 4 and 5 ), and p‐nitrobenzoyl ( 6 and 7 ) groups were synthesized. The best activity was achieved with lycorine esterified at C‐2 position with lauroyl group. Preliminary structure–activity relationship points that unprotected OH group at C‐1 and C‐2 is not necessary to the antiparasitic activity, and none of the derivative was less active than lycorine. The lycorine structural requisites required to kill this amitochondriate cell seem to be different in comparison with the derivatives most active against other parasites and tumor cell lines, both mitochondriated cells. This result is an important contribution with our ongoing studies regarding the mechanism of action of the Amaryllidaceae alkaloids on T. vaginalis cell death opening a new perspective to optimize this innovative pharmacological potential. 相似文献
156.
Reig S Moreno C Moreno D Burdalo M Janssen J Parellada M Zabala A Desco M Arango C 《Schizophrenia bulletin》2009,35(1):233-243
Little is known about the changes that take place in the adolescent brain over the first few years following the onset of psychosis. The present longitudinal study builds on an earlier cross-sectional report demonstrating brain abnormalities in adolescent-onset psychosis patients with a recent-onset first episode of psychosis. Magnetic resonance imaging studies were obtained at baseline and 2 years later from 21 adolescents with psychosis and 34 healthy controls matched for age, gender, and years of education. Whole-brain volumes and gray matter (GM) and cerebrospinal fluid (CSF) volumes of the frontal, parietal, temporal, and occipital lobes were measured at baseline and at 2-year follow-up. In the frontal lobe, the rate of GM volume loss was significantly higher in male patients (2.9% and 2.0%, respectively, for left and right) than in controls (1.2% and 0.7%, respectively, for left and right). In the left frontal lobe, male patients showed a significantly higher rate of CSF volume increase than controls (8.6% vs 6.4%). These differences in rates of volume change were observed in male and female patients, although only males showed significant time x diagnosis interactions. This negative finding in females should be interpreted with caution as the study was underpowered to detect change in women due to limited sample size. An exploratory analysis revealed that schizophrenia and nonschizophrenia psychotic disorders showed similar volume change patterns relative to controls. Change in clinical status was not correlated with longitudinal brain changes. Our results support progression of frontal lobe changes in males with adolescent-onset psychosis. 相似文献
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158.
Dolores Moreno MD Miguel Moreno-Iñiguez MD Dolores Vigil MD Josefina Castro-Fornieles MD Felipe Ortuño MD Ana González-Pinto MD Mara Parellada MD Inmaculada Baeza MD Soraya Otero MD Montserrat Graell MD Ana Aldama MD Celso Arango MD 《European child & adolescent psychiatry》2009,18(3):180-184
There are reports of significant association between obstetric complications (OC) and childhood psychosis. Authors conducted
a case-control study of 102 children and adolescents with a first episode psychosis (FEP) and 94 healthy controls (HC), using
the obstetric complications scale (OCS) and their medical records, to examine the risk of FPE. Patients were recruited from
child and adolescent psychiatry units at six university hospitals and controls from publicly-funded schools of similar characteristics
and from the same geographic areas. A logistic regression was performed to quantify the risk of psychosis in childhood and
adolescence, based on OC, adjusting for potential confounding factors like socio economic status (SES) and family psychiatric
history (FPH). OC appeared more frequently in the records of patients. Significant differences between patients and controls
were found in Prenatal OC (15.7% vs. 5.3%, P < 0.05) and among them, bleeding in pregnancy showed the greatest difference between groups (12.7% vs. 2.1%, P < 0.01). In the logistic regression, bleeding in pregnancy showed a crude odds ratio (OR) of 6.7 (95%CI = 1.4–30.6) and 5.1
(CI 95% = 1.0–24.9) adjusted for SES and FPH. Therefore, bleeding in pregnancy is a likely risk factor for early-onset psychosis. 相似文献
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