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41.
42.
Brown LB Miller WC Kamanga G Kaufman JS Pettifor A Dominik RC Nyirenda N Mmodzi P Mapanje C Martinson F Cohen MS Hoffman IF 《AIDS and behavior》2012,16(5):1148-1155
Provider-assisted methods of partner notification increase testing and counseling among sexual partners of patients diagnosed with HIV, however they are resource-intensive. The sexual partners of individuals enrolled in a clinical trial comparing different methods of HIV partner notification were analyzed to identify who was unlikely to seek testing on their own. Unconditional logistic regression was used to identify partnership characteristics, which were assigned a score based on their coefficient in the final model, and a risk score was calculated for each participant. The risk score included male partner sex, relationship duration 6-24 months, and index education > primary. A risk score of ≥ 2 had a sensitivity of 68% and specificity of 78% in identifying partners unlikely to seek testing on their own. A risk score to target partner notification can reduce the resources required to locate all partners in the community while increasing the testing yield compared to patient-referral. 相似文献
43.
Jessica A. Cintolo M.D. Phyllis Gimotty Ph.D. Anne Blair B.S. DuPont Guerry M.D. David E. Elder M.B. Ch.B. Rachel Hammond M.S. Rosalie Elenitsas M.D. Xiaowei Xu M.D. Ph.D. Douglas Fraker M.D. Lynn M. Schuchter M.D. Brian J. Czerniecki M.D. Ph.D. Giorgos Karakousis M.D. 《Annals of surgical oncology》2013,20(11):3610-3617
Background
Tumor infiltrating lymphocytes (TIL) and histological regression in primary melanoma are generally considered indicators of the local immune response but their roles as prognostic factors have been variably reported. We examined the prognostic role of these variables in patients with high risk (T4) primary melanomas in a large series of patients with long-term follow-up.Methods
From a prospectively maintained cohort of patients diagnosed between 1971 and 2004, 161 patients were retrospectively identified with primary thick melanomas (>4 mm), no clinical evidence of regional nodal disease (RND) at diagnosis and complete histopathologic data. Univariate and multivariate Cox regression models were performed to identify clinical and histopathologic predictors of disease-specific survival (DSS) and to identify subgroups with differential survival.Results
Factors significantly associated with decreased DSS by univariate analysis included male gender, age ≥ 60 years, axial anatomic location, presence of ulceration, RND, absence of TIL, and presence of regression. In the final multivariate model, TIL and regression, as interacting variables, and RND status remained significantly associated with DSS. In the presence of TIL, concomitant regression was associated with significantly worse survival (p ≤ 0.0001). In the absence of TIL, there was no effect of regression on survival (p = 0.324).Conclusions
Primary TIL and regression status and RND status are independently associated with melanoma-specific survival in patients with T4 melanomas; presence of TIL in the primary melanoma with concomitant radial growth phase regression is associated with a poor prognosis and may reflect an ineffective local regional immune response. 相似文献44.
Rosalie M. Grijalva BS Nha Trang Thu Pham BS Qiao Huang PhD Peter R. Martin MS Farwa Ali MD Heather M. Clark PhD Joseph R. Duffy PhD Rene L. Utianski PhD Hugo Botha MD Mary M. Machulda PhD Stephen D. Weigand MS J. Eric Ahlskog PhD MD Dennis W. Dickson MD Keith A. Josephs MD MST MSc Jennifer L. Whitwell PhD 《Movement disorders》2022,37(4):702-712
45.
Arjen M Funhoff Sophie Monge Rosalie Teeuwen Gerben A Koning Nancy M E Schuurmans-Nieuwenbroek Daan J A Crommelin David M Haddleton Wim E Hennink Cornelus F van Nostrum 《Journal of controlled release》2005,102(3):711-724
A combination of A-B and B-C block copolymers was used to encapsulate DNA inside pEG coated particles, where A is a cationic block (poly(dimethylaminoethyl methacrylate), pDMAEMA) for DNA binding and condensation, B is a hydrophobic block (poly(butylmethacrylate), pBMA) and C is a polyethylene glycol (pEG) block. The AB and BC block copolymers were synthesized by transition metal mediated radical polymerization. The AB block copolymer had a fixed pBMA molecular weight of 3800 g/mol and a varying pDMAEMA molecular weight (from 22 to 65 kg/mol), the BC block copolymer had a fixed composition (pBMA 9000 g/mol; pEG 2000 g/mol). Plasmid DNA containing particles were made via a detergent dialysis method. By this method, particles of approximately 120 nm, as determined by dynamic light scattering (DLS), with a near neutral charge were formed, independent of the DMAEMA block size. DLS measurements and gel electrophoresis indicated that the particles were very stable in cell culture medium at 37 degrees C and resistant to anionic exchange by poly-l-aspartic acid. The particles were able to transfect COS-7 and OVCAR-3 cells with minor toxicity if incubated for 1 or 4 h; incubation for 24 h resulted in an increased toxicity. This paper shows that small polyplexes with near neutral charge can be obtained via a convenient detergent dialysis method using pDMAEMA-b-pBMA and pBMA-b-pEG. These particles may be interesting for in vivo experiments where particles with high positive charges have adverse interactions with blood components. 相似文献
46.
K. M. Govaert C. S. van Kessel E. J. A. Steller B. L. Emmink I. Q. Molenaar O. Kranenburg R. van Hillegersberg I. H. M. Borel Rinkes 《Journal of gastrointestinal surgery》2014,18(5):952-960
Aim
To assess the impact of first recurrence location on survival following surgery of colorectal liver metastases.Methods
A total of 265 consecutive patients with colorectal liver metastases undergoing liver surgery (2000–2011) were categorized according to first site of tumor recurrence. Time to recurrence (TTR) and overall survival (OS) were determined. Uni- and multivariate analysis were performed to identify factors associated with TTR and OS.Results
Median TTR was 1.16 years following liver resection, and 0.56 years following radiofrequency ablation (RFA). Intrahepatic recurrence following liver resection resulted in a significantly shorter median TTR compared to extrahepatic recurrence. Intrapulmonary recurrence was associated with superior survival compared to other recurrence locations. Such patterns were not observed in the RFA-treated group. Multivariate analysis identified the type of surgical treatment and extra-hepatic first-site recurrence (other than lung) as independent predictors for OS. Pre-operative chemotherapy and simultaneous intrahepatic and extrahepatic recurrence were independent predictors for both TTR and OS.Conclusions
Patients with intrahepatic recurrence following liver resection have a significantly shorter TTR and OS when compared to patients developing extrahepatic recurrence. Pulmonary recurrence following resection is associated with longer survival. Simultaneous intra- and extrahepatic recurrence is an independent prognostic factor for TTR and OS. 相似文献47.
Peter Molenaar Torsten Christ Emanuel Berk Andreas Engel Katherine T. Gillette Alejandro Galindo-Tovar Ursula Ravens Alberto J. Kaumann 《Naunyn-Schmiedeberg's archives of pharmacology》2014,387(7):629-640
The β-blockers carvedilol and metoprolol provide important therapeutic strategies for heart failure treatment. Therapy with metoprolol facilitates the control by phosphodiesterase PDE3, but not PDE4, of inotropic effects of catecholamines in human failing ventricle. However, it is not known whether carvedilol has the same effect. We investigated whether the PDE3-selective inhibitor cilostamide (0.3 μM) or PDE4-selective inhibitor rolipram (1 μM) modified the positive inotropic and lusitropic effects of catecholamines in ventricular myocardium of heart failure patients treated with carvedilol. Right ventricular trabeculae from explanted hearts of nine carvedilol-treated patients with terminal heart failure were paced to contract at 1 Hz. The effects of (-)-noradrenaline, mediated through β1-adrenoceptors (β2-adrenoceptors blocked with ICI118551), and (-)-adrenaline, mediated through β2-adrenoceptors (β1-adrenoceptors blocked with CGP20712A), were assessed in the absence and presence of the PDE inhibitors. The inotropic potency, estimated from –logEC50s, was unchanged for (-)-noradrenaline but decreased 16-fold for (-)-adrenaline in carvedilol-treated compared to non-β-blocker-treated patients, consistent with the previously reported β2-adrenoceptor-selectivity of carvedilol. Cilostamide caused 2- to 3-fold and 10- to 35-fold potentiations of the inotropic and lusitropic effects of (-)-noradrenaline and (-)-adrenaline, respectively, in trabeculae from carvedilol-treated patients. Rolipram did not affect the inotropic and lusitropic potencies of (-)-noradrenaline or (-)-adrenaline. Treatment of heart failure patients with carvedilol induces PDE3 to selectively control the positive inotropic and lusitropic effects mediated through ventricular β2-adrenoceptors compared to β1-adrenoceptors. The β2-adrenoceptor-selectivity of carvedilol may provide protection against β2-adrenoceptor-mediated ventricular overstimulation in PDE3 inhibitor-treated patients. PDE4 does not control β1- and β2-adrenoceptor-mediated inotropic and lusitropic effects in carvedilol-treated patients. 相似文献
48.
49.
Kelly L. Harris Meagan B. Myers Karen L. McKim Rosalie K. Elespuru Barbara L. Parsons 《Environmental and molecular mutagenesis》2020,61(1):152-175
Cancer driver mutations (CDMs) are necessary and causal for carcinogenesis and have advantages as reporters of carcinogenic risk. However, little progress has been made toward developing measurements of CDMs as biomarkers for use in cancer risk assessment. Impediments for using a CDM-based metric to inform cancer risk include the complexity and stochastic nature of carcinogenesis, technical difficulty in quantifying low-frequency CDMs, and lack of established relationships between cancer driver mutant fractions and tumor incidence. Through literature review and database analyses, this review identifies the most promising targets to investigate as biomarkers of cancer risk. Mutational hotspots were discerned within the 20 most mutated genes across the 10 deadliest cancers. Forty genes were identified that encompass 108 mutational hotspot codons overrepresented in the COSMIC database; 424 different mutations within these hotspot codons account for approximately 63,000 tumors and their prevalence across tumor types is described. The review summarizes literature on the prevalence of CDMs in normal tissues and suggests such mutations are direct and indirect substrates for chemical carcinogenesis, which occurs in a spatially stochastic manner. Evidence that hotspot CDMs (hCDMs) frequently occur as tumor subpopulations is presented, indicating COSMIC data may underestimate mutation prevalence. Analyses of online databases show that genes containing hCDMs are enriched in functions related to intercellular communication. In its totality, the review provides a roadmap for the development of tissue-specific, CDM-based biomarkers of carcinogenic potential, comprised of batteries of hCDMs and can be measured by error-correct next-generation sequencing. Environ. Mol. Mutagen. 61:152–175, 2020. Published 2019. This article is a U.S. Government work and is in the public domain in the USA. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society. 相似文献
50.
Maija P. Valta Hongjuan Zhao Alexandre Ingels Alan E. Thong Rosalie Nolley Matthias Saar Donna M. Peehl 《Clinical & experimental metastasis》2014,31(5):573-584
About one-third of patients with advanced renal cell carcinoma (RCC) have bone metastases. The incidence of RCC is increasing and bone metastatic RCC merits greater focus. Realistic preclinical bone metastasis models of RCC are lacking, hampering the development of effective therapies. We developed a realistic in vivo bone metastasis model of human RCC by implanting precision-cut tissue slices under the renal capsule of immunodeficient mice. The presence of disseminated cells in bone marrow of tissue slice graft (TSG)-bearing mice was screened by human-specific polymerase chain reaction and confirmed by immunohistology using human-specific antibody. Disseminated tumor cells in bone marrow of TSG-bearing mice derived from three of seven RCC patients were detected as early as 1 month after tissue implantation at a high frequency with close resemblance to parent tumors (e.g., CAIX expression and high vascularity). The metastatic patterns of TSGs correlated with disease progression in patients. In addition, TSGs retained capacity to metastasize to bone at high frequency after serial passaging and cryopreservation. Moreover, bone metastases in mice responded to Temsirolimus treatment. Intratibial injections of single cells generated from TSGs showed 100 % engraftment and produced X-ray-visible tumors as early as 3 weeks after cancer cell inoculation. Micro-computed tomography (μCT) and histological analysis revealed osteolytic characteristics of these lesions. Our results demonstrated that orthotopic RCC TSGs have potential to develop bone metastases that respond to standard therapy. This first reported primary RCC bone metastasis model provides a realistic setting to test therapeutics to prevent or treat bone metastases in RCC. 相似文献