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951.
Agelis G Tzioumaki N Tselios T Botić T Cencic A Komiotis D 《European journal of medicinal chemistry》2008,43(7):1366-1375
This report describes the total and facile synthesis of the unsaturated keto and exomethylene pyranonucleoside analogues, 1-(2,3,4-trideoxy-4-methylene-6-O-trityl-alpha-D-glycero-hex-2-enopyranosyl)uracil (10), 1-(2,3-dideoxy-alpha-D-glycero-hex-2-enopyranosyl-4-ulose)uracil (17) and 1-(2,3,4-trideoxy-4-methylene-alpha-D-glycero-hex-2-enopyranosyl)uracil (18). Commercially available 1,2,3,4,6-penta-O-acetyl-alpha-D-mannopyranose (1) was condensed with silylated uracil, deacetylated and acetalated to afford 1-(2,3-O-isopropylidene-alpha-D-mannopyranosyl)uracil (4). Two different synthetic routes were investigated for the conversion of 4 into the olefinic derivative 1-(2,3,4-trideoxy-4-methylene-6-O-trityl-alpha-D-glycero-hex-2-enopyranosyl)uracil (10). Although the two procedures are quite similar with respect to yields and final products, the second also leads to the keto-2',3'-unsaturated analogue (17). The new analogues were evaluated for their anticancer and antiviral activities using several tumor cell lines and gastrointestinal rotavirus. All of the compounds showed direct antiviral effect against rotavirus infectivity in Caco-2 cell line. Moreover, 1-(2,3,4-trideoxy-4-methylene-6-O-trityl-alpha-D-glycero-hex-2-enopyranosyl)uracil (10) was found to be potent in MCF-7 breast carcinoma cell line. 相似文献
952.
A diary study to open up the black box of overtime work among university faculty members 总被引:1,自引:0,他引:1
Beckers DG van Hooff ML van der Linden D Kompier MA Taris TW Geurts SA 《Scandinavian journal of work, environment & health》2008,34(3):213-223
OBJECTIVES: This study aimed at opening up the black box of overtime work among university faculty members by providing information on (i) when faculty members work overtime, (ii) what activities are undertaken during overtime, and (iii) how overtime is experienced. METHODS: Data were collected among 120 Dutch faculty members who completed a general questionnaire (addressing general overtime hours, work characteristics, and well-being) and a 9-day diary study (with information on daily overtime hours, activities, and experiences). Analyses of variance were used to analyze the data. RESULTS: Overtime was very prevalent among faculty members, high overtime workers being nonfatigued, engaged employees with positive work characteristics. Overtime was unevenly distributed over the week, being common on Sunday and Monday and uncommon on Friday and Saturday. Overtime activities during the weekend differed from those during the workweek, relatively much time being spent on research during weekend overtime. Overtime activities were experienced differently than activities during regular hours, overtime work being experienced as less effortful and less stressful than regular workhours and weekend overtime being less pleasurable than regular hours and evening overtime. CONCLUSIONS: This detailed day-to-day mapping and evaluation of overtime work contributes to a better understanding of overtime work by demonstrating meaningful patterns of overtime over the (work)week and meaningful associations between overtime activities and time-contingent experiences. It is suggested that worktime control plays an important role in explaining the results. 相似文献
953.
Thumuluru Kavitha Madhuri Dimitri Papatheodorou Anil Tailor Christopher Sutton Simon Butler-Manuel 《Gynecological surgery》2010,7(4):423-425
We describe the first in vivo use of neutral argon plasma energy in gynaecological surgery in the UK and the largest series worldwide. The use of PlasmaJet® (PJ) in different applications in 118 selected cases in a tertiary referral centre for gynaecological oncology and minimal access surgery was assessed. The effectiveness, ease of use, ergonomics and safety of PJ in gynaecological surgery is evaluated prospectively. Following this experience, we have devised a table of recommended power settings for different applications. 相似文献
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956.
Katrien Verhoeven Geert Crombez Christopher Eccleston Dimitri M.L. Van Ryckeghem Stephen Morley Stefaan Van Damme 《Pain》2010
Research on the effectiveness of distraction as a method of pain control is inconclusive. One mechanism pertains to the motivational relevance of distraction tasks. In this study the motivation to engage in a distraction task during pain was experimentally manipulated. Undergraduate students (N = 73) participated in a cold pressor test (CPT) and were randomly assigned to three groups: a distraction-only group performed a tone-detection task during the CPT, a motivated-distraction group performed the same task and received a monetary reward for good task performance, and a control group did not perform the tone-detection task. Results indicated that engagement in the distraction task was better in the motivated-distraction group in comparison with the distraction-only group. Participants in both distraction groups experienced less pain compared to the control group. There were no overall differences in pain intensity between the two distraction groups. The effect of distraction was influenced by the level of catastrophic thinking about pain. For low catastrophizers, both distraction groups reported less pain as compared to the non-distracted control group. This was not the case for high catastrophizers. For high catastrophizers it mattered whether the distraction task was motivationally relevant: high catastrophizers reported less intense pain in the motivated-distraction group, as compared to the non-distracted control group. We conclude that increasing the motivational relevance of the distraction task may increase the effects of distraction, especially for those who catastrophize about pain. 相似文献
957.
Denisova GF Denisov DA Yeung J Loeb MB Diamond MS Bramson JL 《Molecular immunology》2008,46(1):125-134
Understanding antibody function is often enhanced by knowledge of the specific binding epitope. Here, we describe a computer algorithm that permits epitope prediction based on a collection of random peptide epitopes (mimotopes) isolated by antibody affinity purification. We applied this methodology to the prediction of epitopes for five monoclonal antibodies against the West Nile virus (WNV) E protein, two of which exhibit therapeutic activity in vivo. This strategy was validated by comparison of our results with existing F(ab)-E protein crystal structures and mutational analysis by yeast surface display. We demonstrate that by combining the results of the mimotope method with our data from mutational analysis, epitopes could be predicted with greater certainty. The two methods displayed great complementarity as the mutational analysis facilitated epitope prediction when the results with the mimotope method were equivocal and the mimotope method revealed a broader number of residues within the epitope than the mutational analysis. Our results demonstrate that the combination of these two prediction strategies provides a robust platform for epitope characterization. 相似文献
958.
Julie Tomas Yoon Koo Dimitri Popoff Vilma Arce-Gorvel Sean Hanniffy Jean-Pierre Gorvel Cyrille Mionnet 《Toxins》2021,13(9)
Whooping cough is a severe, highly contagious disease of the human respiratory tract, caused by Bordetella pertussis. The pathogenicity requires several virulence factors, including pertussis toxin (PTX), a key component of current available vaccines. Current vaccines do not induce mucosal immunity. Tissue-resident memory T cells (Trm) are among the first lines of defense against invading pathogens and are involved in long-term protection. However, the factors involved in Trm establishment remain unknown. Comparing two B. pertussis strains expressing PTX (WT) or not (ΔPTX), we show that the toxin is required to generate both lung CD4+ and CD8+ Trm. Co-administering purified PTX with ΔPTX is sufficient to generate these Trm subsets. Importantly, adoptive transfer of lung CD4+ or CD8+ Trm conferred protection against B. pertussis in naïve mice. Taken together, our data demonstrate for the first time a critical role for PTX in the induction of mucosal long-term protection against B. pertussis. 相似文献
959.
Christiane Wesarg Ilya M. Veer Nicole Y. L. Oei Laura S. Daedelow Tristram A. Lett Tobias Banaschewski Gareth J. Barker Arun L.W. Bokde Erin Burke Quinlan Sylvane Desrivires Herta Flor Antoine Grigis Hugh Garavan Rüdiger Brühl JeanLuc Martinot Eric Artiges Frauke Nees Dimitri Papadopoulos Orfanos Luise Poustka Sarah Hohmann Juliane H. Frhner Michael N. Smolka Robert Whelan Gunter Schumann Andreas Heinz Henrik Walter IMAGEN Consortium 《Human brain mapping》2021,42(10):3269
Extensive research has demonstrated that rs1360780, a common single nucleotide polymorphism within the FKBP5 gene, interacts with early‐life stress in predicting psychopathology. Previous results suggest that carriers of the TT genotype of rs1360780 who were exposed to child abuse show differences in structure and functional activation of emotion‐processing brain areas belonging to the salience network. Extending these findings on intermediate phenotypes of psychopathology, we examined if the interaction between rs1360780 and child abuse predicts resting‐state functional connectivity (rsFC) between the amygdala and other areas of the salience network. We analyzed data of young European adults from the general population (N = 774; mean age = 18.76 years) who took part in the IMAGEN study. In the absence of main effects of genotype and abuse, a significant interaction effect was observed for rsFC between the right centromedial amygdala and right posterior insula (p < .025, FWE‐corrected), which was driven by stronger rsFC in TT allele carriers with a history of abuse. Our results suggest that the TT genotype of rs1360780 may render individuals with a history of abuse more vulnerable to functional changes in communication between brain areas processing emotions and bodily sensations, which could underlie or increase the risk for psychopathology. 相似文献
960.
Kupz A Guarda G Gebhardt T Sander LE Short KR Diavatopoulos DA Wijburg OL Cao H Waithman JC Chen W Fernandez-Ruiz D Whitney PG Heath WR Curtiss R Tschopp J Strugnell RA Bedoui S 《Nature immunology》2012,13(2):162-169
Memory T cells exert antigen-independent effector functions, but how these responses are regulated is unclear. We discovered an in vivo link between flagellin-induced NLRC4 inflammasome activation in splenic dendritic cells (DCs) and host protective interferon-γ (IFN-γ) secretion by noncognate memory CD8(+) T cells, which could be activated by Salmonella enterica serovar Typhimurium, Yersinia pseudotuberculosis and Pseudomonas aeruginosa. We show that CD8α(+) DCs were particularly efficient at sensing bacterial flagellin through NLRC4 inflammasomes. Although this activation released interleukin 18 (IL-18) and IL-1β, only IL-18 was required for IFN-γ production by memory CD8(+) T cells. Conversely, only the release of IL-1β, but not IL-18, depended on priming signals mediated by Toll-like receptors. These findings provide a comprehensive mechanistic framework for the regulation of noncognate memory T cell responses during bacterial immunity. 相似文献