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Hardeep Singh Malhotra Ratish Juyal Kiran Preet Malhotra Rakesh Shukla 《Annals of Indian Academy of Neurology》2011,14(1):47-49
Macroglossia is rare in patients of Duchenne muscular dystrophy (DMD), and its occurrence without any endocrinologic abnormality, seizures or an abnormal karyotype is even rarer. We describe a patient of DMD with isolated macroglossia with 271 bp deletion in exon 50 of the dystrophin gene and speculate a relationship in this regard. 相似文献
995.
L Seethalakshmi C Flores R K Malhotra J D Pallias D Tharakan R B Khauli M Menon 《Transplantation》1992,53(1):190-195
We have previously demonstrated that cyclosporine inhibits testosterone (T) biosynthesis in vivo. To better understand the mechanism by which CsA inhibits T synthesis, interstitial cells were isolated from rat testes and incubated in the standard medium 199 with or without CsA (0-10 micrograms/ml) in the presence or absence of human chorionic gonadotropin (hCG, 10(-7) M) and 8-bromo cyclic AMP (cAMP, 0.5 mM) for 3 hr at 32 degrees C. The levels of cAMP and T were determined by RIA. CsA did not inhibit the basal secretion of T, but inhibited hCG-stimulated T production in a dose-dependent manner (4 ng/10(6) cells vs. 10 ng/10(6) cells at a CsA dose of 5 micrograms/ml, P less than 0.05). Radioligand binding of 125I-hLH to testicular membranes was not affected by CsA, as CsA did not compete with hCG/LH for binding sites (25-28% binding with or without CsA). Similarly, the MIX-stimulated cAMP production was not affected by CsA (24.03 +/- 1.09 vs. 20.60 +/- 0.38 pmol/10(6) cells), suggesting that CsA does not inhibit the accumulation of the second messenger. However, when interstitial cells were incubated with CsA in the presence of cAMP, a significant dose-dependent decline in T secretion was observed (7 ng/10(6) cells vs. 20 ng/10(6) cells at a CsA dose of 5 micrograms/ml). To determine whether CsA inhibits the steps beyond cAMP stimulation of T secretion, the kinetic parameters (Km and Vmax) of steroidogenic enzymes, delta 4-3 keto-17 alpha hydroxylase (17 alpha-hydroxylase), and delta 4-3 keto-17 beta hydroxy steroid dehydrogenase (17B-HSD) were determined by using Michaelis Menten analysis. Results are shown in the presence of CsA vs. no CsA: Km and Vmax values for 17 alpha-hydroxylase were (2.32 vs. 7.98 microM) and (27.96 vs. 100.97 pmol/mg protein/min), respectively. For 17B-HSD the Km and Vmax were (2.14 vs. 1.52 microM) and (15 vs. 15 pmol/mg protein/min), respectively. These results indicate that CsA inhibits the activity of 17 alpha-hydroxylase uncompetitively and 17B-HSD activity competitively. In conclusion the primary site for CsA inhibition is the cAMP stimulation and, CsA inhibits T synthesis at multiple sites. 相似文献
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Firoza Mamdani Maureen V. Martin Todd Lencz Brandi Rollins Delbert G. Robinson Emily A. Moon Anil K. Malhotra Marquis P. Vawter 《Disease markers》2013,35(1):11-21
Mood disorders and schizophrenia are common and complex disorders with consistent evidence of genetic and environmental influences on predisposition. It is generally believed that the consequences of disease, gene expression, and allelic heterogeneity may be partly the explanation for the variability observed in treatment response. Correspondingly, while effective treatments are available for some patients, approximately half of the patients fail to respond to current neuropsychiatric treatments. A number of peripheral gene expression studies have been conducted to understand these brain-based disorders and mechanisms of treatment response with the aim of identifying suitable biomarkers and perhaps subgroups of patients based upon molecular fingerprint. In this review, we summarize the results from blood-derived gene expression studies implemented with the aim of discovering biomarkers for treatment response and classification of disorders. We include data from a biomarker study conducted in first-episode subjects with schizophrenia, where the results provide insight into possible individual biological differences that predict antipsychotic response. It is concluded that, while peripheral studies of expression are generating valuable results in pathways involving immune regulation and response, larger studies are required which hopefully will lead to robust biomarkers for treatment response and perhaps underlying variations relevant to these complex disorders. 相似文献
998.
A. Planagumà T. Domenech I. Jover I. Ramos S. Sentellas R. Malhotra M. Miralpeix 《Clinical and experimental immunology》2013,173(2):298-309
Neutrophil recruitment and survival are important control points in the development and resolution of inflammatory processes. 15‐epi‐lipoxin (LX)A4 interaction with formyl peptide receptor 2 (FPR2)/ALX receptor is suggested to enhance anti‐inflammatory neutrophil functions and mediate resolution of airway inflammation. However, it has been reported that 15‐epi‐LXA4 analogues can also bind to cysteinyl leukotriene receptor 1 (CysLT1) and that the CysLT1 antagonist MK‐571 binds to FPR2/ALX, so cross‐reactivity between FPR2/ALX and CysLT1 ligands cannot be discarded. It is not well established whether the resolution properties reported for 15‐epi‐LXA4 are mediated through FPR2/ALX, or if other receptors such as CysLT1 may also be involved. Evaluation of specific FPR2/ALX ligands and CysLT1 antagonists in functional biochemical and cellular assays were performed to establish a role for both receptors in 15‐epi‐LXA4‐mediated signalling and function. In our study, a FPR2/ALX synthetic peptide (WKYMVm) and a small molecule FPR2/ALX agonist (compound 43) induced FPR2/ALX‐mediated signalling, enhancing guanosine triphosphate‐gamma (GTPγ) binding and decreasing cyclic adenosine monophosphate (cAMP) levels, whereas 15‐epi‐LXA4 was inactive. Furthermore, 15‐epi‐LXA4 showed neither binding affinity nor signalling towards CysLT1. In neutrophils, 15‐epi‐LXA4 showed a moderate reduction of interleukin (IL)‐8‐mediated neutrophil chemotaxis but no effect on neutrophil survival was observed. In addition, CysLT1 antagonists were inactive in FPR2/ALX signalling or neutrophil assays. In conclusion, 15‐epi‐LXA4 is not a functional agonist or an antagonist of FPR2/ALX or CysLT1, shows no effect on IL‐8‐induced neutrophil survival and produces only moderate inhibition in IL‐8‐mediated neutrophil migration. Our data do not support an anti‐inflammatory role of 15‐epi‐LXA4‐ FPR2/ALX interaction in IL‐8‐induced neutrophil inflammation. 相似文献
999.
Janella N. Hudson Gwendolyn P. Quinn Lauren E. Wilson Vani N. Simmons 《Journal of cancer education》2018,33(5):1043-1051
Low-dose computed tomography (LDCT) screening is a promising screening modality for increasing the detection rate of early stage lung cancers among high-risk individuals. Despite being recommended by the US Preventative Services Task Force, uptake of LDCT remains low. The objective of the current study was to gather feedback from high-risk consumers and health care providers on LDCT promotional materials. Focus group discussions were conducted with high-risk individuals (8 focus groups; N = 38) and primary care providers (9 focus groups; N = 23). Participants reviewed existing LDCT promotional materials to assess their perceptions of media materials created to publicize LDCT. Data were analyzed using the constant comparative method. Several key themes emerged from focus groups that can be used to inform development of future LDCT promotional materials. High-risk (HR) participants expressed greater receptivity for promotional materials that did not further stigmatize lung cancer and/or smoking and expressed preferences for materials that clearly outlined the risks/benefits of screening. Primary care providers (PCPs) offered suggestions to facilitate the referral process such as diagnostic codes and requested a design that clearly outlined eligibility criteria. A clear and thorough explanation of LDCT eligibility, cost, harms, and benefits was of chief importance for both PCP and HR audiences. Given that PCPs and HR audiences are not well informed on the specifics of LDCT screening eligibility and insurance coverage, creating provider and patient education opportunities will aid in shared decision-making opportunities. Promotional materials that meet the needs of the target audience are needed to facilitate discussions of risks/benefits of screening with HR individuals. 相似文献
1000.
Patel CD Nadig MR Kurien S Barai S Narang R Malhotra A 《Nuclear medicine communications》2006,27(5):425-429
BACKGROUND: Rest gated 201Tl images are considered to be of poor count statistics due to lower energy and low photon flux of 201Tl in addition to increased attenuation and low dose that can be administered. We compared the left ventricular ejection fraction (LVEF), end diastolic (EDV) and end systolic volume (ESV) obtained on 4 h gated rest 201Tl myocardial perfusion single photon emission computed tomography (SPECT) with those obtained by two-dimensional echocardiography (2-D ECHO) in patients with known or suspected coronary artery disease (CAD). METHODS: Eighty-two consecutive patients who underwent gated 201Tl stress-rest myocardial perfusion SPECT and 2-D ECHO were studied. The gated thallium images were processed with Siemens e-soft autocardiac processor and LVEF, EDV and ESV were evaluated using Emory Cardiac Toolbox. The same parameters were also assessed on the 2-D ECHO using the modified Simpson method for comparison. RESULTS: Out of 82 rest gated images, one study was excluded because of poor count statistics. In 81 (99%) patients there was good linear correlation with 2-D ECHO values and rest gated 201Tl SPECT images for EDV, ESV and LVEF. Pearson's correlation co-efficient (r value) for EDV, ESV and LVEF between the two methods was 0.78, 0.79 and 0.88, respectively. A Bland-Altman plot showed close agreement with LVEF but not for EDV and ESV. CONCLUSION: These results suggest that the 4 h rest gated 201Tl study gives a reliable value for the LVEF compared to 2-D ECHO and can be used in routine clinical practice. 相似文献