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991.
Reply letter to Jinnah “Locus pocus” and Albanese “Complex dystonia is not a category in the new 2013 consensus classification”: Necessary evolution,no magic! 下载免费PDF全文
Christine Klein MD Anthony Lang MD Bart P. van de Warrenburg MD Carolyn M. Sue MD PhD Sarah J. Tabrizi MBChB PhD Lars Bertram MD Saadet Mercimek‐Mahmutoglu MD PhD Darius Ebrahimi‐Fakhari MD Thomas T. Warner MD Alexandra Durr MD Birgit Assmann MD Vladimir Kostic MD Katja Lohmann Connie Marras MD PhD International Parkinson Movement Disorder Society Task Force on Classification Nomenclature of Genetic Movement Disorders 《Movement disorders》2016,31(11):1760-1762
992.
Randy P. Auerbach Philippe Mortier Ronny Bruffaerts Jordi Alonso Corina Benjet Pim Cuijpers Koen Demyttenaere David D. Ebert Jennifer Greif Green Penelope Hasking Sue Lee Christine Lochner Margaret McLafferty Matthew K. Nock Maria V. Petukhova Stephanie Pinder‐Amaker Anthony J. Rosellini Nancy A. Sampson Gemma Vilagut Alan M. Zaslavsky Ronald C. Kessler 《International journal of methods in psychiatric research》2019,28(2)
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995.
Ward NJ Buckley SM Waddington SN Vandendriessche T Chuah MK Nathwani AC McIntosh J Tuddenham EG Kinnon C Thrasher AJ McVey JH 《Blood》2011,117(3):798-807
Gene therapy for hemophilia A would be facilitated by development of smaller expression cassettes encoding factor VIII (FVIII), which demonstrate improved biosynthesis and/or enhanced biologic properties. B domain deleted (BDD) FVIII retains full procoagulant function and is expressed at higher levels than wild-type FVIII. However, a partial BDD FVIII, leaving an N-terminal 226 amino acid stretch (N6), increases in vitro secretion of FVIII tenfold compared with BDD-FVIII. In this study, we tested various BDD constructs in the context of either wild-type or codon-optimized cDNA sequences expressed under control of the strong, ubiquitous Spleen Focus Forming Virus promoter within a self-inactivating HIV-based lentiviral vector. Transduced 293T cells in vitro demonstrated detectable FVIII activity. Hemophilic mice treated with lentiviral vectors showed expression of FVIII activity and phenotypic correction sustained over 250 days. Importantly, codon-optimized constructs achieved an unprecedented 29- to 44-fold increase in expression, yielding more than 200% normal human FVIII levels. Addition of B domain sequences to BDD-FVIII did not significantly increase in vivo expression. These significant findings demonstrate that shorter FVIII constructs that can be more easily accommodated in viral vectors can result in increased therapeutic efficacy and may deliver effective gene therapy for hemophilia A. 相似文献
996.
Tami Pilot-Matias Rakesh Tripathi Daniel Cohen Isabelle Gaultier Tatyana Dekhtyar Liangjun Lu Thomas Reisch Michelle Irvin Todd Hopkins Ron Pithawalla Timothy Middleton Teresa Ng Keith McDaniel Yat Sun Or Rajeev Menon Dale Kempf Akhteruzzaman Molla Christine Collins 《Antimicrobial agents and chemotherapy》2015,59(2):988-997
The development of direct-acting antiviral agents is a promising therapeutic advance in the treatment of hepatitis C virus (HCV) infection. However, rapid emergence of drug resistance can limit efficacy and lead to cross-resistance among members of the same drug class. ABT-450 is an efficacious inhibitor of HCV NS3/4A protease, with 50% effective concentration values of 1.0, 0.21, 5.3, 19, 0.09, and 0.69 nM against stable HCV replicons with NS3 protease from genotypes 1a, 1b, 2a, 3a, 4a, and 6a, respectively. In vitro, the most common amino acid variants selected by ABT-450 in genotype 1 were located in NS3 at positions 155, 156, and 168, with the D168Y variant conferring the highest level of resistance to ABT-450 in both genotype 1a and 1b replicons (219- and 337-fold, respectively). In a 3-day monotherapy study with HCV genotype 1-infected patients, ABT-450 was coadministered with ritonavir, a cytochrome P450 3A4 inhibitor shown previously to markedly increase peak, trough, and overall drug exposures of ABT-450. A mean maximum HCV RNA decline of 4.02 log10 was observed at the end of the 3-day dosing period across all doses. The most common variants selected in these patients were R155K and D168V in genotype 1a and D168V in genotype 1b. However, selection of resistant variants was significantly reduced at the highest ABT-450 dose compared to lower doses. These findings were informative for the subsequent evaluation of ABT-450 in combination with additional drug classes in clinical trials in HCV-infected patients. (Study M11-602 is registered at ClinicalTrials.gov under registration no. .) NCT01074008相似文献
997.
Jun-Jae Chung Tobias B. Huber Markus G?del George Jarad Bj?rn Hartleben Christopher Kwoh Alexander Keil Aleksey Karpitskiy Jiancheng Hu Christine J. Huh Marina Cella Richard W. Gross Jeffrey H. Miner Andrey S. Shaw 《The Journal of clinical investigation》2015,125(6):2307-2316
Podocytes are specialized epithelial cells in the kidney glomerulus that play important structural and functional roles in maintaining the filtration barrier. Nephrotic syndrome results from a breakdown of the kidney filtration barrier and is associated with proteinuria, hyperlipidemia, and edema. Additionally, podocytes undergo changes in morphology and internalize plasma proteins in response to this disorder. Here, we used fluid-phase tracers in murine models and determined that podocytes actively internalize fluid from the plasma and that the rate of internalization is increased when the filtration barrier is disrupted. In cultured podocytes, the presence of free fatty acids (FFAs) associated with serum albumin stimulated macropinocytosis through a pathway that involves FFA receptors, the Gβ/Gγ complex, and RAC1. Moreover, mice with elevated levels of plasma FFAs as the result of a high-fat diet were more susceptible to Adriamycin-induced proteinuria than were animals on standard chow. Together, these results support a model in which podocytes sense the disruption of the filtration barrier via FFAs bound to albumin and respond by enhancing fluid-phase uptake. The response to FFAs may function in the development of nephrotic syndrome by amplifying the effects of proteinuria. 相似文献
998.
Claes K Dahan K Tejpar S De Paepe A Bonduelle M Abramowicz M Verellen C Franchimont D Van Cutsem E Kartheuser A 《Acta gastro-enterologica Belgica》2011,74(3):421-426
FAP is characterized by 100-1000s of adenomatous polyps in colon and rectum, and is in 70% of the patients associated with extracolonic manifestations. Attenuated FAP (AFAP) is a less severe form of FAP, marked by the presence of < 100 polyps and a later onset of colorectal cancer (CRC). (A)FAP is caused by autosomal dominantly inherited mutations in the APC (Adenomatous polyposis coli) gene, a tumour suppressor gene that controls beta-catenin turnover in the Wnt pathway. De novo occurrence is reported in 30-40% of the patients. Mutations are detected in 85% of classical FAP families, while only 20%-30% of AFAP cases will exhibit a germline APC mutation. MUTYH is the second (A)FAP-related gene and is involved with base-excision repair of DNA damaged by oxidative stress. MUTYH mutations are inherited in an autosomal recessive way and account for 10%-20% of classical FAP cases without an APC mutation and for 30% of AFAP cases. Genotype-phenotype correlations exist for mutations in the APC gene, however, contradictions in the literature caution against the sole use of the genotype for decisions regarding clinical management. Once the family's specific APC mutation is identified in the proband, predictive testing for first degree relatives is possible from the age of 10 to 12 years on. For AFAP, relatives are tested at age 18 and older. Opinions about the appropriate ages at which to initiate genetic testing may vary. Physicians must have a discussion about prenatal testing with patients in childbearing age. They may either opt for conventional prenatal diagnosis (amniocentesis or chorionic villous sampling) or for preimplantation genetic diagnosis (PGD). 相似文献
999.
Cocuaud C Rodier MH Daniault G Imbert C 《The Journal of antimicrobial chemotherapy》2005,56(3):507-512
OBJECTIVES: Candidiasis can be associated with the formation of biofilms on bioprosthetic surfaces and the intrinsic resistance of Candida albicans biofilms to the most commonly used antifungal agents has been demonstrated. In this study, we report on the antifungal activity of caspofungin at two different concentrations, on C. albicans and Candida parapsilosis biofilms with different ages of maturation. METHODS: Fifteen strains of C. albicans (10 strains susceptible to fluconazole in vitro and five strains resistant to this antifungal agent) and six strains of C. parapsilosis (all were susceptible to fluconazole in vitro) were studied. The antifungal activity of caspofungin was assessed by looking for a significant inhibition of the metabolic activity of yeasts within biofilms. Biofilms of Candida were produced in vitro, on silicone catheters. RESULTS: Caspofungin used at MIC did not modify the metabolic activity of C. albicans, whatever the maturation age of the biofilms. The same concentration of caspofungin significantly reduced the metabolism (P相似文献
1000.
Ralph C. Williams Christine C. Malone John B. Harley 《Arthritis \u0026amp; Rheumatology》1993,36(7):916-926
Objective. To define precise epitopes on human β2-microglobulin (β2m) reacting with polyclonal IgM rheumatoid factors (RF) from patients with rheumatoid arthritis (RA). Methods. Ten polyclonal RF were tested for their human β2m epitope–binding specificities using the entire 99–amino acid sequence synthesized as overlapping 7-mers in an enzyme-linked immunosorbent assay. Glycine substitution for each residue within RF-reacting linear regions was employed to define major reactive sites. Results and Conclusion. Major β2m residues contributing to RF reactivity were tryptophans at positions 60 and 95, lysine at 58, and arginine at position 97. 相似文献