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71.
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Frota Filho JD Lucchese FA Leães P Valente LA Vieira MS Blacher C 《Arquivos brasileiros de cardiologia》2002,78(6):586-591
Cardiac angiosarcomas are malignant tumors that almost invariably have a short and fatal evolution. The therapeutic approach includes surgery, chemotherapy, and radiation therapy, alone or in combination. Heart transplantation is an attractive option in nonresectable tumors, even though the current experience is still limited. However, in most patients, the diagnosis is still established late, and survival is only slightly altered by the proposed treatments, mainly due to previously existing and undetected metastases. We report a case that illustrates the therapeutic dilemma faced with this neoplasia, and we discuss the case based on a literature review. 相似文献
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Guido Torzilli Florin Botea Matteo Donadon Matteo Cimino Fabio Procopio Vittorio Pedicini Dario Poretti Marco Montorsi 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2014,16(11):994-1001
Background
Contrast-enhanced intra-operative ultrasound (CE-IOUS) for colorectal liver metastases (CLMs) has become a part of clinical practice. Whether it should be selectively or routinely applied remains unclear. The aim of this study was to define criteria for the use of CE-IOUS.Methods
One-hundred and twenty-seven patients underwent a hepatectomy for CLMs using IOUS and CE-IOUS. All patients underwent computed tomography (CT) and/or magnetic resonance imaging (MRI) within 2 weeks prior to surgery. The reference was histology, and imaging at 6 months after surgery. Univariate and multivariate analyses were performed. Statistical significance was set at P = 0.05.Results
Using IOUS an additional 172 lesions in 51 patients were found. CE-IOUS found 14 additional lesions in 6 patients. Seventy-eight CLMs in 38 patients appeared within 6 months after surgery. The sensitivity, specificity, positive- and negative-predictive value were 63%, 98%, 100% and 27% for pre-operative imaging, 87%, 100%, 100% and 52% for IOUS, and 89%, 100%, 100% and 56% for IOUS+CE-IOUS, respectively. CE-IOUS allowed better tumour margin definition in 23 patients (18%), thus assisting resection. Analyses indicated that the presence of multiple (P = 0.014), and isoechoic CLMs (P = 0.049) were independently correlated with new findings at CE-IOUS.Conclusions
Compared with IOUS, CE-IOUS improved detection and resection guidance. These additions are significant and demand its use in cases with multiple and isoechoic CLMs. 相似文献76.
Lorenza Di Pascoli Alessra Buja Massimo Bolognesi Sara Montagnese Angelo Gatta Dario Gregori Carlo Merkel 《World journal of gastroenterology : WJG》2014,20(30):10464-10469
AIM:To evaluate the most cost-effectiveness strategy for preventing variceal growth and bleeding in patients with cirrhosis and small esophageal varices.METHODS:A stochastic analysis based on decision trees was performed to compare the cost-effectiveness of beta-blockers therapy starting from a diagnosis of small varices(Strategy 1)with that of endoscopic surveillance followed by beta-blockers treatment when large varices are demonstrated(Strategy 2),for preventing variceal growth,bleeding and death in patients with cirrhosis and small esophageal varices.The basic nodes of the tree were gastrointestinal endoscopy,inpatient admission and treatment for bleeding,as required.All estimates were performed using a Monte Carlo microsimulation technique,consisting in simulating observations from known probability distributions depicted in the model.Eight-hundred-thousand simulations were performed to obtain the final estimates.All estimates were then subjected to Monte Carlo Probabilistic sensitivity analysis,to assess the impact of the variability of such estimates on the outcome distributions.RESULTS:The event rate(considered as progression of varices or bleeding or death)in Strategy 1[24.09%(95%CI:14.89%-33.29%)]was significantly lower than in Strategy 2[60.00%(95%CI:48.91%-71.08%)].The mean cost(up to the first event)associated with Strategy 1[823£(95%CI:106£-2036£)]was not significantly different from that of Strategy 2[799£(95%CI:0£-3498£)].The cost-effectiveness ratio with respect to this endpoint was equal to 50.26£(95%CI:-504.37£-604.89£)per event avoided over the four-year follow-up.When bleeding episodes/deaths in subjects whose varices had grown were included,the mean cost associated with Strategy 1 was 1028£(95%CI:122£-2581£),while 1699£(95%CI:171£-4674£)in Strategy 2.CONCLUSION:Beta-blocker therapy turn out to be more effective and less expensive than endoscopic surveillance for primary prophylaxis of bleeding in patients with cirrhosis and small varices. 相似文献
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Andrea E. Steuer Justine Raeber Christian Steuer Martina I. Boxler Dario A. Dornbierer Oliver G. Bosch Boris B. Quednow Erich Seifritz Thomas Kraemer 《Drug testing and analysis》2019,11(6):813-823
Gamma‐hydroxybutyrate (GHB) is a short‐chain fatty acid that occurs naturally in the mammalian brain and is prescribed as a medication against narcolepsy or used as a drug of abuse. Particularly, its use as a knock‐out drug in cases of drug‐facilitated crimes is of major importance in forensic toxicology. Because of its rapid metabolism and resulting narrow detection windows (<12 hours in urine), detection of GHB remains challenging. Thus, there is an urgent call for new markers to improve the reliable detection of GHB use. In the framework of a randomized, placebo‐controlled, crossover study in 20 healthy male volunteers, urine samples obtained 4.5 hours post‐administration were submitted to untargeted mass spectrometry [MS, quadrupole time of flight (QTOF)] analysis to identify possible new markers of GHB intake. MS data from four different analytical methods (reversed phase and hydrophilic interaction liquid chromatography; positive and negative electrospray ionization) were filtered for significantly changed features applying univariate and multivariate statistics. From the resulting 42 compounds of interest, 8 were finally identified including conjugates of GHB with carnitine, glutamate, and glycine as well as the endogenous compounds glycolate and succinylcarnitine. While GHB conjugates were only detectable in the GHB, but not in the placebo group, glycolate and succinylcarnitine were present in both groups albeit significantly increased through GHB intake. Untargeted metabolomics proved as a suitable tool for the non‐hypothesis driven identification of new GHB markers. However, more studies on actual concentrations, detection windows, and stability will be necessary to assess the suitability of these markers for routine application. 相似文献
79.
Matteo Ballottari Marcelo J. P. Alcocer Cosimo D’Andrea Daniele Viola Tae Kyu Ahn Annamaria Petrozza Dario Polli Graham R. Fleming Giulio Cerullo Roberto Bassi 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(23):E2431-E2438
In oxygenic photosynthetic eukaryotes, the hydroxylated carotenoid zeaxanthin is produced from preexisting violaxanthin upon exposure to excess light conditions. Zeaxanthin binding to components of the photosystem II (PSII) antenna system has been investigated thoroughly and shown to help in the dissipation of excess chlorophyll-excited states and scavenging of oxygen radicals. However, the functional consequences of the accumulation of the light-harvesting complex I (LHCI) proteins in the photosystem I (PSI) antenna have remained unclarified so far. In this work we investigated the effect of zeaxanthin binding on photoprotection of PSI–LHCI by comparing preparations isolated from wild-type Arabidopsis thaliana (i.e., with violaxanthin) and those isolated from the A. thaliana nonphotochemical quenching 2 mutant, in which violaxanthin is replaced by zeaxanthin. Time-resolved fluorescence measurements showed that zeaxanthin binding leads to a previously unrecognized quenching effect on PSI–LHCI fluorescence. The efficiency of energy transfer from the LHCI moiety of the complex to the PSI reaction center was down-regulated, and an enhanced PSI resistance to photoinhibition was observed both in vitro and in vivo. Thus, zeaxanthin was shown to be effective in inducing dissipative states in PSI, similar to its well-known effect on PSII. We propose that, upon acclimation to high light, PSI–LHCI changes its light-harvesting efficiency by a zeaxanthin-dependent quenching of the absorbed excitation energy, whereas in PSII the stoichiometry of LHC antenna proteins per reaction center is reduced directly.In eukaryotic photosynthetic organisms, photosystem I (PSI) and photosystem II (PSII) comprise a core complex hosting cofactors involved in electron transport and an outer antenna system made of light-harvesting complexes (LHCs): Lhcas for PSI and Lhcbs for PSII. The core complexes bind chlorophyll a (Chl a) and β-carotene, whereas the outer antenna system, in addition to Chl a, binds chlorophyll b (Chl b) and xanthophylls. Despite their overall similarity, PSI and PSII differ in the rate at which they trap excitation energy at the reaction center (RC), with PSI being faster than PSII (1–9). They also differ in their structure (10–12). PSI is monomeric and carries its antenna moiety on only one side as a half-moon–shaped structure whose size is not modulated by growth conditions (13, 14). PSII, on the other hand, is found mainly as a dimeric core surrounded by an inner layer of antenna proteins (Lhcb4–6) and an outer layer of heterotrimeric LHCII complexes (Lhcb 1–3) whose stoichiometry varies depending on the growth conditions (7, 12, 13, 15). Acclimation to high irradiance leads to a lower number of trimers per PSII RC accompanied by loss of the monomeric Lhcb6. These slow acclimative responses regulate the excitation pressure on the PSII RC, preventing saturation of the electron transport chain (16) and the oxidative stress in high light (HL), leading to photoinhibition. The response to rapid changes in light level is managed by turning on some photoprotective mechanisms, such as the nonphotochemical quenching (NPQ) of the excess energy absorbed by PSII (16), which is activated by the acidification of the thylakoid lumen and protonation of the trigger protein PsbS or LhcSR. Low luminal pH also activates violaxanthin de-epoxidase (VDE), catalyzing the de-epoxidation of the xanthophyll violaxanthin to zeaxanthin (17, 18), a scavenger of reactive oxygen species (ROS) produced by excess light (9, 13). Zeaxanthin also enhances NPQ, as observed in vivo by a decrease of PSII fluorescence (19). The short-term effects of exposure to HL on PSI have been disregarded thus far. Because of its rapid photochemistry, PSI shows low fluorescence emission, implying a low 1Chl* concentration and a low probability that chlorophyll triplet states will be formed by intersystem crossing. This characteristic suggests that the formation of oxygen singlet excited states (1O*2) is reduced and that NPQ phenomena in photoprotection are less relevant in PSI (20, 21). Nevertheless, several reports have shown that, especially in the cold (22–29), PSI can exhibit photo-inhibition, with its Lhca proteins being the primary target (24, 30). Upon synthesis in HL, zeaxanthin binding could be traced to two different types of binding site. One, designated “V1,” is located in the periphery of LHCII trimers (31–33). The second, designated “L2,” has an inner location in the dimeric Lhca1–4 and the monomeric Lhcb4–6 members of the LHC family (34–37). Experimental determination of the efficiency of the violaxanthin-to-zeaxanthin exchange yielded a maximal score in the Lhca3 and Lhca4 subunits (24, 25). Interestingly, Lhca1/4 and Lhca2/3 are bound to the PSI core as dimers that can be isolated in fractions identified as “LHCI-730” and “LHCI-680,” respectively, both accumulating zeaxanthin to a de-epoxidation index of ∼0.2 (20, 38). Lhca3 and Lhca4 carry low-absorption-energy chlorophyll forms known as “red forms” (39, 40) that are responsible for the red-shifted PSI emission peak at 730–740 nm at 77 K. The molecular basis for red forms is an excitonic interaction of two chromophores: chlorophylls 603 and 609 located a few angstroms from the xanthophyll in site L2, which can be either violaxanthin or zeaxanthin depending on light conditions (41, 42). It is unclear whether the binding of zeaxanthin to the PSI–LHCI complex has specific physiological function(s) or is simply a result of its common origin with Lhcb proteins.The goal of this study was to understand whether zeaxanthin plays a role in PSI–LHCI photoprotection. To investigate the role of zeaxanthin bound to Lhca proteins, we analyzed the changes in antenna size and Chl a fluorescence dynamics in PSI supercomplexes binding either violaxanthin or zeaxanthin. We found a zeaxanthin-dependent regulation of PSI antenna size and an enhanced resistance to excess light upon zeaxanthin binding. These results show that dynamic changes in the efficiency of light use and in photoprotection capacity are not exclusive to PSII, as previously thought; instead, eukaryotic photosynthetic organisms modulate the function of both photosystems in a coordinated manner. 相似文献