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11.
Neil E Martin Thomas B Brunner Krystina D Kiel Thomas F DeLaney William F Regine Mohammed Mohiuddin Ernest F Rosato Daniel G Haller James P Stevenson Debbie Smith Barnali Pramanik Joel Tepper Wesley K Tanaka Briggs Morrison Paul Deutsch Anjali K Gupta Ruth J Muschel W Gillies McKenna Eric J Bernhard Stephen M Hahn 《Clinical cancer research》2004,10(16):5447-5454
PURPOSE: Preclinical and clinical studies have demonstrated that inhibition of prenylation can radiosensitize cell lines with activation of Ras and produce clinical response in patients with cancer. The aim of this study was to determine the maximally tolerated dose of the dual farnesyltransferase and geranylgeranyltransferase I inhibitor L-778,123 in combination with radiotherapy for patients with locally advanced pancreatic cancer. EXPERIMENTAL DESIGN: L-778,123 was given by continuous intravenous infusion with concomitant radiotherapy to 59.4 Gy in standard fractions. Two L-778,123 dose levels were tested: 280 mg/m2/day over weeks 1, 2, 4, and 5 for dose level 1; and 560 mg/m2/day over weeks 1, 2, 4, 5, and 7 for dose level 2. RESULTS: There were no dose-limiting toxicities observed in the eight patients treated on dose level 1. Two of the four patients on dose level 2 experienced dose-limiting toxicities consisting of grade 3 diarrhea in one case and grade 3 gastrointestinal hemorrhage associated with grade 3 thrombocytopenia and neutropenia in the other case. Other common toxicities were mild neutropenia, dehydration, hyperglycemia, and nausea/vomiting. One patient on dose level 1 showed a partial response of 6 months in duration. Both reversible inhibition of HDJ2 farnesylation and radiosensitization of a study patient-derived cell line were demonstrated in the presence of L-778,123. K-RAS mutations were found in three of the four patients evaluated. CONCLUSIONS: The combination of L-778,123 and radiotherapy at dose level 1 showed acceptable toxicity in patients with locally advanced pancreatic cancer. Radiosensitization of a patient-derived pancreatic cancer cell line was observed. 相似文献
12.
Anjali Shinde Charles T Mehlman Margaret H Collins 《Pediatric and developmental pathology》2006,9(1):38-43
Recently, clonal chromosome abnormalities have been identified in the mural spindle cells in aneurysmal bone cysts (ABCs), but the nature of the cystic spaces is unclear. Endothelial injury has been suggested as a mechanism of aneurysmal formation in these lesions, but few studies have surveyed vascular markers in ABCs. We stained 25 primary aneurysmal bone cysts with a variety of antibodies that stain vessels. Antibody to factor 8 stained the edge of ABC cavities in almost all cases, and antibodies to VEGF-C, GLUT-1, and smooth muscle actin stained the edge of the cavities in approximately half the cases. Antibodies to D2-40 and CD34 also stained the edge of the cavities in some cases. These results suggest that the cavities in ABCs are related to vasculature and support the theory that vascular injury may be important in the pathogenesis of ABCs. 相似文献
13.
Manisha Nada D Rohit SV Singh AK Khurana Sakshi Lochab Anjali Kharolia 《Indian journal of ophthalmology》2022,70(11):3854
Purpose:Incisions in cataract surgery can be modified in various ways in terms of size, shape, and axis to reduce or tailor astigmatism. This study was conducted to examine the effect of site (superior vs, temporal) and shape (frown vs. V-shaped, chevron) of scleral incisions for cataract surgery on corneal curvature.Methods:The prospective study was carried out on 200 consecutive patients with senile cataract and who were planned for surgery at a tertiary eye hospital in north India. The placement of the incision was decided by the steeper corneal meridian—whether superior or temporal—and then patients of these two groups were randomized for frown and V-shaped incision; in this way, four groups of 50 patients each were formed. Follow-up was done on day 1, at 2 weeks, 4 weeks, 8 weeks, and 12 weeks. At each follow-up, post-operative keratometry with routine postoperative examination was done. The results were statistically analyzed by using student’s t-test, Chi-squared test, and the Pearson correlation coefficient.Results:In all the four groups, the difference of preoperative astigmatism and surgically-induced astigmatism was statistically highly significant. The analysis of uncorrected visual acuity (UCVA) was statistically significant (P < 0.05) on postoperative day 1 and at 2, 4, and 12 postoperative weeks; it was statistically insignificant (P > 0.05) at postoperative week 8.Conclusion:Temporal incisions result in lesser postoperative surgically induced astigmatism (SIA) than superior incisions. Chevron incisions result in minimal change in corneal curvature. This effect can be utilized to tailor the postoperative astigmatism. 相似文献
14.
Kanchan Singh Prashant Bhushan Deepak Mishra Kirandeep Kaur Bharat Gurnani Anjali Singh Swasti Pandey 《Indian journal of ophthalmology》2022,70(12):4152
Purpose:The current study was aimed at assessment of optic disk by disk damage likelihood scale (DDLS) staging using slit-lamp biomicroscopy and optical coherence tomography (OCT) in diagnosing primary open-angle glaucoma (POAG) patients.Methods:This was a cross-sectional observational study of 106 POAG patients, which was conducted from April 2017 to April 2018. All patients underwent slit-lamp fundoscopy with a +78 D lens and high-definition (HD)-OCT, and the vertical cup disk ratios (VCDRs) were recorded. Disk size and neuroretinal rim assessment were done, and the disk was then staged using the recent version, which stages the optic nerve head (ONH) from 1 to 10 as read from the DDLS nomogram table. DDLS scores >5 indicate glaucomatous damage. Pearson coefficient was used to correlate the DDLS staging by slit-lamp biomicroscopy with best-corrected visual acuity (BCVA), intraocular pressure (IOP), disk size, and VCDR and VCDR, mean deviation, and DDLS staging by HD-OCT.Results:The mean age of the patients was 59.54 ± 6.61 years. The male: female ratio was 2:1. The mean IOP was 16.04 ± 1.97 mmHg, and BCVA was 0.72 ± 0.13 LogMAR units. The mean VCDR on 78 D slit-lamp biomicroscopy was 0.76 ± 0.09 (standard deviation [SD]) (range 0.1–0.77), whereas on HD-OCT, the mean VCDR was 0.81 ± 0.09 (SD) (range 0.07–0.81). The mean deviation on visual field testing in decibels was −14.43 ± 3.31 (SD). The correlation coefficient between DDLS staging by slit-lamp biomicroscopy and DDLS staging by HD-OCT parameters was r = 0.96.Conclusion:There is a positive correlation between the DDLS system of optic disk evaluation on slit-lamp biomicroscopy and most of the HD-OCT evaluation parameters. 相似文献
15.
Arian Khorshid Anjali Wignarajah Jiaqi Zhang Ruben Alvero Ruth B. Lathi Barry Behr Gayathree Murugappan 《Journal of assisted reproduction and genetics》2023,40(1):153
Purpose To explore perceptions towards embryo disposition among patients donating excess embryos to a research biobank.MethodsCross-sectional study of survey responses collected as part of enrollment in a research biobank. Patients are asked questions regarding the difficulty of their disposition decision, their alternative disposition choice if donation to research was not available, quality of the counseling they received, and if additional counseling throughout their treatment would have been beneficial. Survey responses use 5-point Likert scales, with “1” being lowest/least and “5” being highest/most.ResultsA total of 157 men and 163 women enrolled in the biobank. Median scores for difficulty of disposition decision were 3 for females and 2 for males, and for quality of counseling, the median scores were 4 for females and 3 for males. Seventy percent of patients would have chosen to discard their excess embryos had donation to research not been an option. Statistical analyses showed no significant difference in responses based on variations in race, religion, sexual orientation, and infertility diagnoses. Concordance of responses within heterosexual couples was tested and found to be poor to moderate.ConclusionsAssessing patients’ perceptions towards embryo disposition after donation of their excess embryos to a research biobank affords a unique perspective. The difficulty of the disposition decision, the tendency to discard embryos in the absence of a means for donation to research, and the poor agreement between heterosexual partners highlight the importance of donation to research as an accessible disposition option and the need for a personalized approach to counseling and consenting for embryo disposition.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10815-022-02659-x.Keyword: Embryo disposition 相似文献
16.
Christina L. Nemeth
zgül Gk Sophia N. Tomlinson Anjali Sharma Ann B. Moser Sujatha Kannan Rangaramanujam M. Kannan Ali Fatemi 《Neurotherapeutics》2023,20(1):272
X-linked adrenoleukodystrophy (ALD) is a genetic disorder that presents neurologically as either a rapid and fatal cerebral demyelinating disease in childhood (childhood cerebral adrenoleukodystrophy; ccALD) or slow degeneration of the spinal cord in adulthood (adrenomyeloneuropathy; AMN). All forms of ALD result from mutations in the ATP Binding Cassette Subfamily D Member (ABCD) 1 gene, encoding a peroxisomal transporter responsible for the import of very long chain fatty acids (VLCFA) and results mechanistically in a complex array of dysfunction, including endoplasmic reticulum stress, oxidative stress, mitochondrial dysfunction, and inflammation. Few therapeutic options exist for these patients; however, an additional peroxisomal transport protein (ABCD2) has been successfully targeted previously for compensation of dysfunctional ABCD1. 4-Phenylbutyrate (4PBA), a potent activator of the ABCD1 homolog ABCD2, is FDA approved, but use for ALD has been stymied by a short half-life and thus a need for unfeasibly high doses. We conjugated 4PBA to hydroxyl polyamidoamine (PAMAM) dendrimers (D-4PBA) to a create a long-lasting and intracellularly targeted approach which crosses the blood–brain barrier to upregulate Abcd2 and its downstream pathways. Across two studies, Abcd1 knockout mice administered D-4PBA long term showed neurobehavioral improvement and increased Abcd2 expression. Furthermore, when the conjugate was administered early, significant reduction of VLCFA and improved survival of spinal cord neurons was observed. Taken together, these data show improved efficacy of D-4PBA compared to previous studies of free 4PBA alone, and promise for D-4PBA in the treatment of complex and chronic neurodegenerative diseases using a dendrimer delivery platform that has shown successes in recent clinical trials. While recovery in our studies was partial, combined therapies on the dendrimer platform may offer a safe and complete strategy for treatment of ALD.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-022-01311-x. 相似文献
17.
Stimulation of adrenergic activity by desipramine enhances hematopoietic stem and progenitor cell mobilization along with G‐CSF in multiple myeloma: A pilot study 下载免费PDF全文
Aditi Shastri Anjali Budhathoki Stefan K. Barta Noah Kornblum Olga Derman Ramakrishna Battini Radha Raghupathy Amit K. Verma Paul S. Frenette Ira Braunschweig Murali Janakiram 《American journal of hematology》2017,92(10):1047-1051
Hematopoietic stem cell (HSC) release is positively regulated by the sympathetic nervous system through the β3 adrenergic receptor. Preclinical studies have demonstrated that the combination of desipramine and G‐CSF resulted in improved HSC mobilization. Here, we present the results of an open‐label single‐arm pilot study in patients with multiple myeloma undergoing autologous stem cell transplantation (ASCT) to assess the safety and efficacy of desipramine combined with G‐SCF to induce HSC mobilization. The primary endpoint was safety of the combination including engraftment kinetics. The secondary endpoint was the proportion of patients who collected ≥5 × 106 CD34+ cells/kg. Outcomes were compared with historical matched controls during the same time period with multiple myeloma mobilized with G‐CSF. All study patients received desipramine 100 mg daily for 7 days, starting 4 days prior to G‐CSF administration (D‐3) and continued taking it along with G‐CSF for a total of 7 days. Six of ten patients enrolled completed the protocol with minimal side effects. All of them achieved the target collection of 5 × 106 CD34 cells/kg in a median of 1.5 apheresis session with two patients needing additional plerixafor (16%), while 11 out of 13 patients (85%) achieved the target of 5 × 106 CD34 cells/kg in the historical control group in a median of 2 apheresis procedures and seven patients needed plerixafor (54%). The combination of desipramine and G‐CSF is safe and signals improved mobilization over G‐CSF alone, providing a possible alternative means of mobilization that needs further investigation. 相似文献
18.
ObjectiveTo estimate butyrylcholinesterase (BChE), phosphodiesterase (PDE), thiols and cerulopalsmin by non – invasive means in saliva a of subjects (both cases and controls) and correlated to their hearing sensitivity.MethodsTotal of 13 subjects participated in this study. Among them 7 were having auditory neuropathy and 6 were healthy controls. Unstimulated saliva (10 ml) was collected from each participant. Ceruloplasmin, thiols, phosphodiesterase and pseudocholinesterase were estimated by colorimetric method in the salivary samples.ResultsSalivary BChE and PDE levels were marginally elevated and protein thiols were marginally decreased in cases as compared to that of controls. Salivary ceruloplasmin was significantly decreased (p = 0.022) in cases as compared to that of controls.ConclusionsSaliva can be used as a potential noninvasive tool for evaluation of disorders. 相似文献
19.
Pulmonary hypertension: Barrier or just a bump in the road in transplanting adults with congenital heart disease 下载免费PDF全文
Jonathan N. Menachem MD Edo Y. Birati MD Payman Zamani MD Anjali T. Owens MD Pavan Atluri MD Christian A. Bermudez MD David Drajpuch NP Stephanie Fuller MD Yuli Y. Kim MD Christopher E. Mascio MD Vikram Palanivel MD J. Eduardo Rame MD Joyce Wald DO Michael A. Acker MD Jeremy A. Mazurek MD 《Congenital heart disease》2018,13(4):492-498
20.