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BACKGROUND AND PURPOSE: In 1990 the skin source measuring bridge was proposed as a tool to measure (1) the distance between the interstitial implant and the overlying skin during brachytherapy boost treatment as well as (2) the distances between the lateral source end and the exit point of the guide needle. The present study reports on the clinical experience using the source skin measuring bridge with respect to incidence and grade of teleangiectasia, and their relation to source skin distances and doses. PATIENTS AND METHODS: Two hundred and twenty-two breast cancer patients (229 breasts) treated between 1983 and 1996 with breast conserving therapy including a brachytherapy boost were scored on the occurrence of teleangiectasia. The minimum distance between the sources (above implant and laterally) and the skin surface were measured. RESULTS: If no bridge was used the appearance of teleangiectasia in the epiderm above the implant is 77, 63 and 50% for boost doses of 25, 20 and 15 Gy, respectively. For brachytherapy boost doses of 25 and 20 Gy and distances smaller than 10mm between the implant and the overlying epiderm, as determined with the skin source measuring bridge, the appearance of teleangiectasia was 78 and 46%, respectively. When respecting provisional dosimetry to spare the skin for a boost dose of 15 Gy, resulting in distances between 10 and 15 mm for the implant overlying skin and distances between 5 and 10 mm for the lateral skin, teleangiectasia can be reduced to a minimum (6.3% above and 3.3% laterally). While in a univariate analysis several parameters (use of the bridge, boost dose, boost modality, external beam therapy modality) were predictive factors, the use of the bridge remained the only significant variable in a multivariate analysis. CONCLUSIONS: The skin source measuring bridge reduces teleangiectasia after interstitial brachytherapy boost treatment. A hypothesis made previously relating teleangiectasia and source skin distances was verified and extended. Even when 3D planning is used, the bridge allows for a provisional calculation of the security margins between source positions and the skin at the time of BT implantation to assure a correct needle positioning from the beginning, instead of correcting dwell times later on to avoid unnecessary high skin doses. 相似文献
95.
Interleukin-1 and interleukin-6 gene polymorphisms and the risk of breast cancer in caucasian women. 总被引:7,自引:0,他引:7
Lukas A Hefler Christoph Grimm Tilmann Lantzsch Dieter Lampe Sepp Leodolter Heinz Koelbl Georg Heinze Alexander Reinthaller Dan Tong-Cacsire Clemens Tempfer Robert Zeillinger 《Clinical cancer research》2005,11(16):5718-5721
PURPOSE: Genetic polymorphisms of cytokine-encoding genes are known to predispose to malignant disease. Interleukin (IL)-1 and IL-6 are crucially involved in breast carcinogenesis. Whether polymorphisms of the genes encoding IL-1 (IL1) and IL-6 (IL6) also influence breast cancer risk is unknown. EXPERIMENTAL DESIGN: In the present case-control study, we ascertained three polymorphisms of the IL1 gene cluster [-889 C/T polymorphism of the IL1alpha gene (IL1A), -511 C/T polymorphism of the IL1beta promoter (IL1B promoter), a polymorphism of IL1beta exon 5 (IL1B exon 5)], an 86-bp repeat in intron 2 of the IL1 receptor antagonist gene (IL1RN), and the -174 G/C polymorphism of the IL6 gene (IL6) in 269 patients with breast cancer and 227 healthy controls using PCR and pyrosequencing. RESULTS: Polymorphisms within the IL1 gene cluster and the respective haplotypes were not associated with the presence and the phenotype of breast cancer. The IL6 polymorphism was significantly associated with breast cancer. Odds ratios for women with one or two high-risk alleles versus women homozygous for the low-risk allele were 1.5 (95% confidence interval, 1.04-2.3; P = 0.04) and 2.0 (95% confidence interval, 1.1-3.6; P = 0.02), respectively. No association was ascertained between presence of the IL6 polymorphism and various clinicopathologic variables. CONCLUSIONS: Although polymorphisms within the IL1 gene cluster do not seem to influence breast cancer risk or phenotype, presence of the -174C IL6 allele increases the risk of breast cancer in Caucasian women in a dose-dependent fashion. 相似文献
96.
Ajmal Zarinwall Viktor Maurer Jennifer Pierick Victor Marcus Oldhues Julian Cedric Porsiel Jan Henrik Finke Georg Garnweitner 《Drug delivery》2022,29(1):2086
Promising active pharmaceutical ingredients (APIs) often exhibit poor aqueous solubility and thus a low bioavailability that substantially limits their pharmaceutical application. Hence, efficient formulations are required for an effective translation into highly efficient drug products. One strategy is the preservation of an amorphous state of the API within a carrier matrix, which leads to enhanced dissolution. In this work, mesoporous silica aerogels (SA) were utilized as a carrier matrix for the amorphization of the poorly water-soluble model drug ibuprofen. Loading of tailored SA was performed post-synthetically and solvent-free, either by co-milling or via the melting method. Thorough analyses of these processes demonstrated the influence of macrostructural changes during the drying and grinding process on the microstructural properties of the SA. Furthermore, interfacial SA-drug interaction properties were selectively tuned by attaching terminal hydrophilic amino- or hydrophobic methyl groups to the surface of the gel. We demonstrate that not only the chemical surface properties of the SA, but also formulation-related parameters, such as the carrier-to-drug ratio, as well as process-related parameters, such as the drug loading method, decisively influence the ibuprofen adsorption efficiency. In addition, the drug-loaded SA formulations exhibited a remarkable physical stability over a period of 6 months. Furthermore, the release behavior is shown to change considerably with different surface properties of the SA matrix. Hence, the reported results demonstrate that utilizing specifically processed and modified SA offers a compelling technique for enhancement of the bioavailability of poorly-water soluble APIs and a versatile adjustment of their release profile. 相似文献
97.
Ulrich Hegerl Roland Mergl Christian Sander Jens Dietzel Istvan Bitter Koen Demyttenaere Ricardo Gusmão Ana González-Pinto Iñaki Zorrilla Adriana García Alocén Victor Perez Sola Eduard Vieta Georg Juckel Ulrich S. Zimmermann Michael Bauer Pascal Sienaert Sónia Quintão Marc-Andreas Edel Michael Kluge 《European neuropsychopharmacology》2018,28(1):185-194
Based on many clinical and preclinical findings the ‘vigilance regulation model of mania’ postulates that an unstable regulation of wakefulness is a pathogenetic factor in both mania and Attention Deficit Hyperactivity Disorder (ADHD) and induces hyperactivity and sensation seeking as an autoregulatory attempt to stabilize wakefulness. Accordingly, stimulant medications with their vigilance stabilizing properties could have rapid antimanic effects similar to their beneficial effects in ADHD. The MEMAP study – a multi-center, double-blind, placebo-controlled and randomized clinical trial (RCT) – assessed the antimanic efficacy and safety of a 2.5-day treatment with methylphenidate (20–40 mg/day). Of 157 screened patients with acute mania, 42 were randomly assigned to receive 20–40 mg per day of methylphenidate in one or two applications, or placebo. The primary outcome was the change in Young Mania Rating Scale (YMRS) sum scores from baseline to day 2.5 in the methylphenidate group compared to the placebo group. A group sequential design was chosen to justify early RCT termination based on efficacy or futility at an interim analysis after inclusion of 40 patients. In the interim analysis, the change from baseline in the YMRS total score at day 2.5 was not significantly different between both groups (F(1,37)=0.23; p=0.64). Thus, futility was declared for methylphenidate and the RCT was stopped. In summary, although methylphenidate was well tolerated and safe in the full analysis set, it failed to show efficacy in the treatment of acute mania. Trial registration: clinicaltrials.gov (URL: http://www.clinicaltrials.gov; registration number: NCT01541605). 相似文献
98.
Philipp Saiko Geraldine Graser Benedikt Giessrigl Andreas Lackner Michael Grusch Georg Krupitza Arijit Basu Barij Nayan Sinha Venkatesan Jayaprakash Walter Jaeger Monika Fritzer-Szekeres Thomas Szekeres 《Biochemical pharmacology》2011,(1):50
Ribonucleotide reductase (RR; EC 1.17.4.1) is responsible for the de novo conversion of ribonucleoside diphosphates into deoxyribonucleoside diphosphates, which are essential for DNA replication. RR is upregulated in tumor cells and therefore considered to be an excellent target for cancer chemotherapy.ABNM-13 (N-hydroxy-2-(anthracene-2-yl-methylene)-hydrazinecarboximidamide), a novel N-hydroxy-N′-aminoguanidine has been designed to inhibit RR activity using 3D molecular space modeling techniques. In this study, we evaluated its effect on human HL-60 promyelocytic leukemia cells. ABNM-13 proved to be a potent inhibitor of RR which was displayed by significant alterations of deoxyribonucleoside triphosphate (dNTP) pool balance and a highly significant decrease of incorporation of radiolabeled cytidine into DNA of HL-60 cells. Diminished RR activity caused replication stress which was consistent with activation of Chk1 and Chk2, resulting in downregulation/degradation of Cdc25A. In contrast, Cdc25B was upregulated, leading to dephosphorylation and activation of Cdk1. The combined disregulation of Cdc25A and Cdc25B was the most likely cause for ABNM-13 induced S-phase arrest. Finally, we combined ABNM-13 with the first-line antileukemic agent arabinofuranosylcytosine (Ara-C) and found that ABNM-13 synergistically potentiated the antineoplastic effects of Ara-C.Due to these promising results, ABNM-13 deserves further preclinical and in vivo testing. 相似文献
99.
Holmes D Alpers GW Ismailji T Classen C Wales T Cheasty V Miller A Koopman C 《Violence against women》2007,13(11):1192-1205
This study examined relationships between cognitive and emotional processing with changes in pain and depression among intimate partner violence survivors. Twenty-five women who wrote about their most traumatic experiences completed measures of pain and depressive symptoms before the first writing session and again 4 months following the last writing session. Reduced pain was significantly associated with less use of positive and negative emotion words. Relationships between cognitive and emotional aspects of writing with changes in depressive symptoms fell short of statistical significance. The results suggest that emotional processing in narrative writing predicts changes in pain in intimate partner violence survivors. 相似文献
100.
Georg Walther 《Journal of molecular medicine (Berlin, Germany)》1949,27(1-2):22-24
Zusammenfassung 1. Der Ersatz des Sublimats in derHayemschen Lösung durch Zinkchlorid oder Kupfer (2)-chlorid liefert Reagentien, welche für die Anstellung von Serumflockungsreaktionen in gleicher Weise geeignet sind wie dieHayemsche Lösung selbst. Die mit den neuen Modifikationen erhaltenen Ergebnisse unterscheiden sich praktisch nicht von denjenigen mit der Originalmethode. Für alle 3 Lösungen ist der Satz gültig, daß eine beginnende Serumflockung nach Zusatz von weniger als 0,2–0,3 cm3 meist gleichbedeutend mit einer positiven Takatareaktion ist.2. Eisenchloridlösungen sind zum Ersatz des Sublimats in derHayem-Lösung für den Zweck der Serumflockung wenig geeignet, die Chloride von Strontium, Barium, Cadmium, Magnesium, Calcium, Zinn, Blei, Aluminium und Kalium völlig unbrauchbar. 相似文献