全文获取类型
收费全文 | 3536篇 |
免费 | 319篇 |
国内免费 | 30篇 |
专业分类
耳鼻咽喉 | 42篇 |
儿科学 | 76篇 |
妇产科学 | 28篇 |
基础医学 | 517篇 |
口腔科学 | 40篇 |
临床医学 | 386篇 |
内科学 | 708篇 |
皮肤病学 | 51篇 |
神经病学 | 273篇 |
特种医学 | 189篇 |
外科学 | 582篇 |
综合类 | 39篇 |
一般理论 | 1篇 |
预防医学 | 249篇 |
眼科学 | 95篇 |
药学 | 254篇 |
中国医学 | 1篇 |
肿瘤学 | 354篇 |
出版年
2023年 | 17篇 |
2022年 | 32篇 |
2021年 | 134篇 |
2020年 | 70篇 |
2019年 | 107篇 |
2018年 | 135篇 |
2017年 | 79篇 |
2016年 | 101篇 |
2015年 | 92篇 |
2014年 | 123篇 |
2013年 | 156篇 |
2012年 | 265篇 |
2011年 | 273篇 |
2010年 | 136篇 |
2009年 | 109篇 |
2008年 | 193篇 |
2007年 | 195篇 |
2006年 | 178篇 |
2005年 | 158篇 |
2004年 | 137篇 |
2003年 | 118篇 |
2002年 | 112篇 |
2001年 | 73篇 |
2000年 | 65篇 |
1999年 | 45篇 |
1998年 | 35篇 |
1997年 | 31篇 |
1996年 | 33篇 |
1995年 | 32篇 |
1994年 | 27篇 |
1993年 | 28篇 |
1992年 | 43篇 |
1991年 | 54篇 |
1990年 | 63篇 |
1989年 | 61篇 |
1988年 | 44篇 |
1987年 | 29篇 |
1986年 | 28篇 |
1985年 | 26篇 |
1984年 | 15篇 |
1983年 | 14篇 |
1982年 | 20篇 |
1980年 | 16篇 |
1979年 | 15篇 |
1978年 | 14篇 |
1977年 | 15篇 |
1974年 | 15篇 |
1973年 | 17篇 |
1971年 | 12篇 |
1970年 | 9篇 |
排序方式: 共有3885条查询结果,搜索用时 531 毫秒
121.
Olivier Ferlatte Travis Salway Hottes Terry Trussler Rick Marchand 《AIDS and behavior》2014,18(7):1256-1263
Syndemic has become an important theoretical model toward understanding how psychosocial issues may interact to increase HIV acquisition among gay and bisexual men. We measured the extent to which anti-gay experiences are associated with psychosocial issues, which in turn were hypothesized to have an additive effect on HIV risk, in a sample of Canadian young gay and bisexual men. Sixty-eight percent of men reported at least one form of anti-gay experience. For each additional form of anti-gay experience, our data demonstrated increased likelihood of psychosocial issues. Psychosocial issues had an additive effect, increasing the risk of unprotected intercourse in the last 12 months (doubling the risk for those with 3+ issues OR 1.95 [1.39–2.75]). Overall, our findings suggest that a syndemic is occurring among young Canadian gay and bisexual men, highlighting the need to expand HIV prevention efforts beyond sexual risk, to address stigma and gay men’s broader health concerns. 相似文献
122.
Benjamin Poh Paul Cashin Kaye Bowers Travis Ackermann Yeng Kwang Tay Arun Dhir Daniel Croagh 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2014,16(7):629-634
Introduction
Minimally-invasive options for the management of choledocholithiasis in patients undergoing laparoscopic cholecystectomy include laparoscopic and endoscopic approaches. This study reviews the effectiveness of both approaches in an emergency setting.Methods
A retrospective chart review was performed for a cohort of patients who underwent laparoscopic cholecystectomy. Outcomes assessed were duct clearance, the number of procedures performed (NPP), length of stay (LOS) and complication rate.Results
A total of 182 patients who underwent emergency laparoscopic cholecystectomies received intervention for choledocholithiasis. The duct clearance rate was lower in the laparoscopic group, 63% versus 86% (P = 0.001). However, the median NPP was also lesser in the laparoscopic group, 1 (interquartile range (IQR) 1–2) versus 2 (IQR 2–2) (P < 0.001), as was the median LOS, 5 days (IQR 3–8) versus 7 days (IQR 6–10) (P = 0.009). Forty-eight laparoscopic endobiliary stents were attempted; stent deployment was successful in 37 patients. A larger proportion of patients with laparoscopic endobiliary stents had duct clearance by endoscopic retrograde cholangiopancreatography (ERCP) compared with those without, although this was not statistically significant (P = 0.208).Conclusion
Laparoscopic clearance is not as effective as post-operative ERCP in an emergency cohort, but is associated with fewer procedures required and a shorter inpatient stay. Thus, laparoscopic clearance may still be an attractive option for surgeons especially where conditions are favourable during an emergency laparoscopic cholecystectomy. 相似文献123.
124.
Lisa M. Lorenz Valerie M. Toomey Adam C. Lanzarotta Rick A. Flurer Travis M. Falconer 《Drug testing and analysis》2019,11(7):1109-1115
A liquid chromatography‐mass spectrometry (LC–MS) screen for known anabolic‐androgenic steroids in a dietary supplement product marketed for “performance enhancement” detected an unknown compound having steroid‐like spectral characteristics. The compound was isolated using high performance liquid chromatography with ultraviolet detection (HPLC–UV) coupled with an analytical scale fraction collector. After the compound was isolated, it was then characterized using gas chromatography with simultaneous Fourier Transform infrared detection and mass spectrometry (GC–FT–IR–MS), liquid chromatography–high resolution accurate mass–mass spectrometry (LC–HRAM–MS) and nuclear magnetic resonance (NMR). The steroid had an accurate mass of m/z 285.1847 (error?0.57 ppm) for the protonated species [M + H]+, corresponding to a molecular formula of C19H24O2. Based on the GC–FT–IR–MS data, NMR data, and accurate mass, the compound was identified as androsta‐3,5‐diene‐7,17‐dione. Although this is not the first reported identification of this designer steroid in a dietary supplement, the data provided adds information for identification of this compound not previously reported. This compound was subsequently detected in another dietary supplement product, which contained three additional active ingredients. 相似文献
125.
126.
Daozhou Gao Abdou Amza Baidou Nassirou Boubacar Kadri Nicholas Sippl-Swezey Fengchen Liu Sarah F. Ackley Thomas M. Lietman Travis C. Porco 《The American journal of tropical medicine and hygiene》2014,91(5):936-942
Mass administration of azithromycin for trachoma has been shown to reduce malarial parasitemia. However, the optimal seasonal timing of such distributions for antimalarial benefit has not been established. We performed numerical analyses on a seasonally forced epidemic model (of Ross-Macdonald type) with periodic impulsive annual mass treatment to address this question. We conclude that when azithromycin-based trachoma elimination programs occur in regions of seasonal malaria transmission, such as Niger, the optimal seasonal timing of mass drug administration (MDA) may not occur during the season of maximum transmission. 相似文献
127.
Joanna J. Kaylor Jeremy D. Cook Jacob Makshanoff Nicholas Bischoff Jennifer Yong Gabriel H. Travis 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(20):7302-7307
Absorption of a photon by a rhodopsin or cone-opsin pigment isomerizes its 11-cis-retinaldehyde (11-cis-RAL) chromophore to all-trans-retinaldehyde (all-trans-RAL), which dissociates after a brief period of activation. Light sensitivity is restored to the resulting apo-opsin when it recombines with another 11-cis-RAL. Conversion of all-trans-RAL to 11-cis-RAL is carried out by an enzyme pathway called the visual cycle in cells of the retinal pigment epithelium. A second visual cycle is present in Müller cells of the retina. The retinol isomerase for this noncanonical pathway is dihydroceramide desaturase (DES1), which catalyzes equilibrium isomerization of retinol. Because 11-cis-retinol (11-cis-ROL) constitutes only a small fraction of total retinols in an equilibrium mixture, a subsequent step involving selective removal of 11-cis-ROL is required to drive synthesis of 11-cis-retinoids for production of visual chromophore. Selective esterification of 11-cis-ROL is one possibility. Crude homogenates of chicken retinas rapidly convert all-trans-ROL to 11-cis-retinyl esters (11-cis-REs) with minimal formation of other retinyl-ester isomers. This enzymatic activity implies the existence of an 11-cis-specific retinyl-ester synthase in Müller cells. Here, we evaluated multifunctional O-acyltransferase (MFAT) as a candidate for this 11-cis-RE-synthase. MFAT exhibited much higher catalytic efficiency as a synthase of 11-cis-REs versus other retinyl-ester isomers. Further, we show that MFAT is expressed in Müller cells. Finally, homogenates of cells coexpressing DES1 and MFAT catalyzed the conversion of all-trans-ROL to 11-cis-RP, similar to what we observed with chicken-retina homogenates. MFAT is therefore an excellent candidate for the retinyl-ester synthase that cooperates with DES1 to drive synthesis of 11-cis-retinoids by mass action.Light perception begins with the absorption of a photon by an opsin pigment in the membranous outer segment (OS) of a rod or cone photoreceptor cell. The light-absorbing chromophore in most vertebrate opsins is 11-cis-retinaldehyde (11-cis-RAL). Photon capture isomerizes the 11-cis-RAL to all-trans-retinaldehyde (all-trans-RAL), inducing conformational changes in the protein that lead to its active meta-II state. After a brief period of signaling through the transduction cascade, meta II decays to yield apo-opsin and free all-trans-RAL. Light sensitivity is restored to the apo-opsin when it combines with 11-cis-RAL to regenerate the pigment. Conversion of all-trans-RAL to 11-cis-RAL is carried out by a multistep enzyme pathway called the visual cycle, located in cells of the retinal pigment epithelium (RPE) (1, 2). The retinoid isomerase in this pathway is Rpe65, which converts an all-trans-retinyl ester (all-trans-RE), such as all-trans-retinyl palmitate (all-trans-RP), to 11-cis-retinol (11-cis-ROL) and a free fatty acid (3–5). Retinyl esters are synthesized in RPE cells by lecithin:retinol acyl transferase (LRAT), which transfers a fatty acid from phosphatidylcholine to retinol (6, 7). LRAT converts both all-trans-ROL and 11-cis-ROL to their cognate esters with similar catalytic efficiency (8).A second visual cycle is present in Müller cells of the retina, providing 11-cis-ROL to cones (9–11). Cones, but not rods, can use 11-cis-ROL as a chromophore precursor to regenerate bleached opsin pigments (10, 12, 13). The isomerase in the noncanonical pathway is dihydroceramide desaturase (DES1) (11). DES1 catalyzes rapid equilibrium isomerization of retinol (11). At equilibrium, 11-cis-ROL is much less abundant than all-trans-ROL, due to the 4.1 kcal/mole difference in free energy between these isomers (14). Accordingly, a secondary source of energy is required to drive the conversion of all-trans-ROL to 11-cis-ROL by DES1. Retinas from cone-dominant species contain 11-cis-retinyl esters (11-cis-REs), whereas retinyl esters are much less abundant in retinas from rod-dominant species (11, 13, 15). Homogenates from cone-dominant chicken and ground-squirrel retinas convert all-trans-ROL predominantly to 11-cis-REs in the presence of palmitoyl CoA (palm CoA) (13, 16, 17). These observations suggest that selective esterification of 11-cis-ROL may be the driving force for 11-cis-retinoid formation. In the current work, we sought to identify the protein responsible for the 11-cis-RE-synthase activity in Müller cells. We evaluated multifunctional O-acyltransferase (MFAT) as a candidate for this synthase. MFAT, also called acyl-CoA wax-alcohol acyltransferase-2 (AWAT2), catalyzes palm CoA-dependent synthesis of triglycerides, wax monoesters, and retinyl esters (18). It is present in the endoplasmic reticulum and predominantly expressed in skin (18). The retinol-isomer specificity of MFAT, and its expression in ocular tissues, has not been studied. 相似文献
128.
Davidson KC Adams AM Goodson JM McDonald CE Potter JC Berndt JD Biechele TL Taylor RJ Moon RT 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(12):4485-4490
Signal transduction pathways play diverse, context-dependent roles in vertebrate development. In studies of human embryonic stem cells (hESCs), conflicting reports claim Wnt/β-catenin signaling promotes either self-renewal or differentiation. We use a sensitive reporter to establish that Wnt/β-catenin signaling is not active during hESC self-renewal. Inhibiting this pathway over multiple passages has no detrimental effect on hESC maintenance, whereas activating signaling results in loss of self-renewal and induction of mesoderm lineage genes. Following exposure to pathway agonists, hESCs exhibit a delay in activation of β-catenin signaling, which led us to postulate that Wnt/β-catenin signaling is actively repressed during self-renewal. In support of this hypothesis, we demonstrate that OCT4 represses β-catenin signaling during self-renewal and that targeted knockdown of OCT4 activates β-catenin signaling in hESCs. Using a fluorescent reporter of β-catenin signaling in live hESCs, we observe that the reporter is activated in a very heterogeneous manner in response to stimulation with Wnt ligand. Sorting cells on the basis of their fluorescence reveals that hESCs with elevated β-catenin signaling express higher levels of differentiation markers. Together these data support a dominant role for Wnt/β-catenin signaling in the differentiation rather than self-renewal of hESCs. 相似文献
129.
S McGowan AM Buckle MS Mitchell JT Hoopes DT Gallagher RD Heselpoth Y Shen CF Reboul RH Law VA Fischetti JC Whisstock DC Nelson 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(31):12752-12757
Bacteriophages deploy lysins that degrade the bacterial cell wall and facilitate virus egress from the host. When applied exogenously, these enzymes destroy susceptible microbes and, accordingly, have potential as therapeutic agents. The most potent lysin identified to date is PlyC, an enzyme assembled from two components (PlyCA and PlyCB) that is specific for streptococcal species. Here the structure of the PlyC holoenzyme reveals that a single PlyCA moiety is tethered to a ring-shaped assembly of eight PlyCB molecules. Structure-guided mutagenesis reveals that the bacterial cell wall binding is achieved through a cleft on PlyCB. Unexpectedly, our structural data reveal that PlyCA contains a glycoside hydrolase domain in addition to the previously recognized cysteine, histidine-dependent amidohydrolases/peptidases catalytic domain. The presence of eight cell wall-binding domains together with two catalytic domains may explain the extraordinary potency of the PlyC holoenyzme toward target bacteria. 相似文献
130.