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71.
72.
KA Hodgkinson SP Connors N Merner A Haywood T‐L Young WJ McKenna B Gallagher F Curtis AS Bassett PS Parfrey 《Clinical genetics》2013,83(4):321-331
To determine the phenotype and natural history of a founder genetic subtype of autosomal dominant arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by a p.S358L mutation in TMEM43. The age of onset of cardiac symptoms, clinical events and test abnormalities were studied in 412 subjects (258 affected and 154 unaffected), all of which occurred in affected males significantly earlier and more often than unaffected males. Affected males were hospitalized four times more often than affected females (p ≤ 0.0001) and died younger (p ≤ 0.001). The temporal sequence from symptoms onset to death was prolonged in affected females by 1–2 decades. The most prevalent electrocardiogram (ECG) manifestation was poor R wave progression (PRWP), with affected males twice as likely to develop PRWP as affected females (p ≤ 0.05). Left ventricular enlargement (LVE) occurred in 43% of affected subjects, with 11% fulfilling criteria for dilated cardiomyopathy. Ventricular ectopy on Holter monitor was common and occurred early: the most diagnostically useful clinical test. No symptom or test could rule out diagnosis. This ARVC subtype is a sex‐influenced lethal arrhythmogenic cardiomyopathy, with a unique ECG finding, LV dilatation, heart failure and early death, where molecular pre‐symptomatic diagnosis has the greatest clinical utility. 相似文献
73.
Connor WJ Bevington Ju-Chieh Cheng Ivan S Klyuzhin Mariya V Cherkasova Catharine A Winstanley Vesna Sossi 《Journal of cerebral blood flow and metabolism》2021,41(1):116
Current methods using a single PET scan to detect voxel-level transient dopamine release—using F-test (significance) and cluster size thresholding—have limited detection sensitivity for clusters of release small in size and/or having low release levels. Specifically, simulations show that voxels with release near the peripheries of such clusters are often rejected—becoming false negatives and ultimately distorting the F-distribution of rejected voxels. We suggest a Monte Carlo method that incorporates these two observations into a cost function, allowing erroneously rejected voxels to be accepted under specified criteria. In simulations, the proposed method improves detection sensitivity by up to 50% while preserving the cluster size threshold, or up to 180% when optimizing for sensitivity. A further parametric-based voxelwise thresholding is then suggested to better estimate the release dynamics in detected clusters. We apply the Monte Carlo method to a pilot scan from a human gambling study, where additional parametrically unique clusters are detected as compared to the current best methods—results consistent with our simulations. 相似文献
74.
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Amy L. Gentzler Meagan A. Ramsey Katelyn R. Black 《Attachment & human development》2013,15(4):376-398
This study investigated how mothers’ attachment was related to their responses to their own and their children’s positive events and positive affect (PA). Ninety-seven mothers reported on their attachment and their responses to their own and their 7–12-year-old children’s positive events and emotions. Children reported on their mothers’ responses to the children’s positive events and their attachment security with their mothers. The results indicated that more avoidant mothers reported less intense PA in response to their own and their children’s positive events. More avoidant mothers also were less likely to encourage their children to savor positive events (through expressing PA, reflecting on PA or themselves, giving rewards, and affectionate responses). Mothers higher on anxiety reported greater likelihood of dampening (e.g., minimizing the event’s importance) their own positive events and reported being more likely to feel discomfort and to reprimand their children for expressing PA. Children’s security was predicted by mothers’ lower likelihood of encouraging children’s dampening and of reprimanding children for PA displays. This study advances the literature on how mothers’ attachment is related to the ways in which they regulate their own and their children’s PA, which may have implications for children’s attachment and developing PA regulation. 相似文献
76.
Tom De Beule T Boulanger S Heye WJ van Rooij WH van Zwam L Stockx 《Interventional neuroradiology》2021,27(1):51
Background and purposeFlow diverters are increasingly used to treat intracranial aneurysms. We report the safety and efficacy of the p64 flow diverter, a resheathable and detachable device for intracranial aneurysms.Materials and methodsWe retrospectively reviewed 108 patients with 109 aneurysms treated with the p64 between March 2014 and July 2019. There were 87 women and 21 men, mean age 57 years. Of 109 aneurysms, 74 were discovered incidentally, 12 were symptomatic, 18 were previously treated, and five were ruptured dissection aneurysms. A total of 10 aneurysms were located in the posterior circulation. The mean aneurysm or remnant size was 8.1 mm.ResultsHemorrhage by perforation with the distal guidewire occurred in two patients with permanent neurological deficits in one. In one patient, acute in-stent occlusion caused infarction with a permanent deficit. Permanent morbidity was 1.9% (2 of 108, 95%CI 0.1–6.9%); there was no mortality. During follow-up, three in-stent occlusions occurred, all asymptomatic. There were no delayed hemorrhagic complications. At six months, 77 of 96 aneurysms (80.2%) were completely occluded, and at last follow-up, this increased to 93 of 96 aneurysms (96.9%). In-stent stenosis at any degree occurred in 11 patients, progressing to asymptomatic complete occlusion in one. In the other patients, stenosis resolved or improved at further follow-up.ConclusionThe p64 offers an effective and safe treatment option. Aneurysm occlusion rate was 97% at last follow-up, mostly achieved with a single device. There were no delayed hemorrhagic complications. Delayed in-stent stenosis infrequently progresses to occlusion but remains a matter of concern. 相似文献
77.
Structural Brain Changes following Long-Term 6° Head-Down Tilt Bed Rest as an Analog for Spaceflight
D.R. Roberts X. Zhu A. Tabesh E.W. Duffy D.A. Ramsey T.R. Brown 《AJNR. American journal of neuroradiology》2015,36(11):2048
BACKGROUND AND PURPOSE:Following long-term spaceflight, a subset of the National Aeronautics and Space Administration astronauts present with visual impairment and increased intracranial pressure, known as visual impairment and intracranial pressure syndrome. We investigated structural brain changes following long-term head-down tilt bed rest as a spaceflight analog.MATERIALS AND METHODS:Volumetric analysis was performed on structural pre- and post–bed rest brain MR images.RESULTS:Comparing post–bed rest to pre–bed rest images, we found the following: 1) no significant group differences in GM, WM, CSF, or ventricular volumes; 2) shift of the center of mass of the brain upward and posterior rotation of the brain relative to the skull; 3) a significant correlation between posterior brain rotation and changes in ventricular volume; and 4) significant increases in brain tissue density in regions at the vertex, including the frontoparietal lobes, with contraction of adjacent extra-axial CSF spaces, and significant decreases in tissue density in areas along the base of the brain, including the orbitofrontal cortex.CONCLUSIONS:We observed widespread morphologic changes with brain tissue redistribution in response to gravity changes; possible associated functional changes are unknown. The observation that ventricular change is correlated to posterior brain rotation suggests an alteration in CSF homeostasis. Ultimately, to elucidate any structural changes that may play a role in visual impairment and intracranial pressure syndrome, volumetric analysis of pre- and postflight structural scans of astronauts is needed.Following long-term missions aboard the International Space Station, increased intracranial pressure and papilledema have been documented in the National Aeronautics and Space Administration (NASA) astronauts. In 1 report1 investigating 7 astronauts following 6 months of spaceflight, all astronauts demonstrated ophthalmologic findings, with disc edema in 5 astronauts and globe flattening in 5. Lumbar punctures were performed in 4 of these astronauts with opening pressures of 21–28.5 cm H2O1. In the 1 astronaut who underwent repeated lumbar punctures, the opening pressure remained elevated 19 months following spaceflight at 22 cm H2O1. The etiology of these findings is currently unclear; however, it has been hypothesized that they may result from loss of gravitational hydrostatic pressure gradients and large cephalad fluid shifts. NASA has coined the term “visual impairment and intracranial pressure [VIIP] syndrome” to describe this constellation of signs and symptoms in astronauts and has likened VIIP syndrome to Earth-based idiopathic intracranial hypertension (IIH) or pseudotumor cerebri.A traditional ground-based analog used by NASA and other international space agencies to study physiologic changes associated with long-term spaceflight has been to place healthy subjects in 6° head-down tilt bed rest for varying periods.2,3 Anecdotally, Russian scientists first devised the head-down-tilt protocol in the early 1970s on the basis of reports by Russian cosmonauts who had the sensation of slipping off the foot of the bed on return to Earth after long-duration missions.3 The foot of the bed was raised until it felt horizontal to help the cosmonauts sleep.3 As an analog for spaceflight, the reduction in Gz gravitational stimuli during bed rest results in an upward shift of body fluids, unloading the upright weight of the body, reduced work against the force of gravity, and lower extremity inactivity.3 As a result, many of the physiologic changes of spaceflight can be reproduced, including decreased cardiac output, orthostatic intolerance, muscle atrophy, and bone loss. This model has been applied extensively to investigate cardiovascular and musculoskeletal deconditioning, immunologic response, and cognitive functioning.2,3We previously acquired structural MR imaging brain scans of subjects participating in a NASA-sponsored long-term bed rest study.4 Given the recent interest in intracranial adaptation to spaceflight, we decided to perform a volumetric analysis of the structural MR imaging dataset to assess any potential alterations in brain structure or CSF distribution that may shed light on the spectrum of findings noted in VIIP syndrome. The results of this analysis are presented here. 相似文献
78.
CXCR4 is a chemokine receptor required for hematopoietic stem cell engraftment and B-cell development. This study found that a small fraction of primitive CD34(+)/CD19(+) B-cell progenitors do not express CXCR4. These CD34(+)/CD19(+)/CXCR4(-) cells were also remarkable for the relative lack of primitive myeloid or lymphoid surface markers. When placed in B-lymphocyte culture conditions these cells matured to express CXCR4 and other surface antigens characteristic of B cells. Surprisingly, when placed in a myeloid culture environment, the CXCR4(-) B-cell progenitors could differentiate into granulocyte, macrophage, and erythroid cells at a high frequency. These data define a novel B-cell/myeloid common progenitor (termed the BMP) and imply a less restrictive pathway of myeloid versus lymphoid development than previously postulated. 相似文献
79.
Purified populations of natural killer (NK) cells were obtained from mice with severe combined immune deficiency (SCID). SCID spleen cells were cultured and activated with recombinant human interleukin-2 (rhIL- 2) in vitro. The activated NK cells were then transferred with syngeneic BALB/c bone marrow cells (BMC) and rhIL-2 into lethally irradiated syngeneic recipients to determine their effect on long-term hematopoietic reconstitution. On analysis, the transfer of rhIL-2- activated NK cells along with BMC resulted in significant increases in splenic and BM hematopoietic progenitor cells when compared with those for mice not receiving NK cells. Histologic and flow cytometric analysis showed a marked increase in granulocytic and megakaryocytic lineage cells present in the spleens of the mice receiving activated NK cells. Analysis of the peripheral blood indicated that the transfer of activated NK cells with BMC also significantly improved platelet and total white blood cell counts, with increases in segmented neutrophils. Erythroid recovery was not affected. Finally, lethally irradiated mice receiving activated NK cells and rhIL-2 along with limiting numbers of syngeneic BMC showed a marked increase in survival rate. These results show that the use of populations enriched for activated NK cells after syngeneic BM transplantation (BMT) has a profound enhancing effect on engraftment primarily affecting megakaryocytic and granulocytic cell reconstitution. Therefore, the transfer of activated NK cells and rhIL- 2 may be of clinical use to promote hematopoietic reconstitution after BMT. 相似文献