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Severe microcephaly was present from birth in a child with a 13q-chromosomal syndrome [46,XY,del(13)(q22q31)]. He died at 20 months of age. Neuropathologic findings included atelencephaly and eosinophilic cytoplasmic inclusions in cerebellar Purkinje cells. Ultrastructurally, the inclusions consisted of stacks of parallel cisternae separated by electron-dense granular material. The relationship between these inclusions and the smaller cytoplasmic inclusions known as "lamellar bodies" is discussed, and the central nervous system malformations in this syndrome are reviewed. 相似文献
94.
Sharshar T Hopkinson NS Ross ET Jonville S Dayer MJ Nickol AH Lofaso F Moxham J Polkey MI 《Respiratory physiology & neurobiology》2005,146(1):5-19
The costal and crural parts of the diaphragm differ in their embryological development and physiological function. It is not known if this is reflected in differences in their motor cortical representation. We compared the response of the costal and crural diaphragms using varying intensities of transcranial magnetic stimulation of the motor cortex at rest and during submaximal and maximal inspiratory efforts. The costal and crural motor evoked potential recruitment curves during submaximal inspiratory efforts were similar. The response to stimulation before, during and at 10 and 30 min after 44 consecutive maximal inspiratory efforts was also the same. Using paired stimulations to investigate intra-cortical facilitatory and inhibitory circuits we found no difference between the costal and crural response with varying interstimulus intervals, or when conditioning and test stimulus intensity were varied. We conclude that supraspinal control of the costal and crural diaphragm is identical during inspiratory tasks. 相似文献
95.
Serengulam V Govindan Gary L Griffiths Rhona Stein Philip Andrews Robert M Sharkey Hans J Hansen Ivan D Horak David M Goldenberg 《Journal of nuclear medicine》2005,46(1):153-159
Radiolabeling of monoclonal antibodies (mAbs) with an intracellularly trapped form of (131)I (residualizing (131)I) involves radioiodinating a small molecular entity, conjugating it to the mAb, and purification. Column purifications are impractical during procedures involving multi-gigabecquerel levels of radioactivity. The goal of this study was to develop a simple, remote, "1-pot" method of radiolabeling and purification for the scaled-up radioiodination of a humanized anti-carcinoembryonic antigen (CEA) mAb, humanized MN-14 (hMN-14; labetuzumab), with an optimized residualizing (131)I moiety, (131)I-IMP-R4. IMP-R4 is MCC-Lys(MCC)-Lys(X)-d-Tyr-d-Lys(X)-OH, where MCC is 4-(N-maleimidomethyl)-cyclohexane-1-carbonyl and X is 1-((4-thiocarbonylamino)benzyl)-diethylenetriaminepentaacetic acid. METHODS: An IODO-GEN-based remote labeling system was used. IMP-R4 was radioiodinated (0.13 mumol per 3.7 GBq of (131)I) at a pH of 7.0-7.4 and conjugated to disulfide-reduced hMN-14 after quenching of unused reactive (131)I. The product was purified by stirring for 5 min with a 20% (w/v) suspension of an anion-exchange resin and sterilely filtered into a sealed vial. Human serum albumin was added at a final concentration of 1%-2.5%. Immunoreactivity was determined by mixing with CEA and determining the complexation level by size-exclusion high-pressure liquid chromatography. Two control radiolabelings, either with unreduced hMN-14 or with IMP-R4 omitted, also were performed. RESULTS: In 18 radiolabelings with (131)I in the range of 2.04-4.81 GBq (55-130 mCi), yields of 59.9% +/- 7.9% (mean +/- SD) at specific activities of 200 +/- 26 MBq/mg (5.4 +/- 0.7 mCi/mg) were obtained, with > or =95% of the radioactivity being associated with hMN-14 and with < or =4% aggregation. Similar yields were obtained in a subset of radiolabelings (n = 7) with >3.7 GBq of (131)I. The immunoreactivities of the preparations were typically >95%. Nonspecific incorporation in the absence of IMP-R4 was 0.5%, whereas that obtained with unreduced IgG was approximately 8%, possibly because of conjugation of IMP-R4 at lysine sites. The process also removed >99% of the quenching reagent used. Radiolabelings performed with freshly prepared solutions or lyophilized preparations produced similar yields, a result that suggested the option for a single-use kit design. CONCLUSION: Efficient removal of (131)I-IMP-R4 and quenched (131)I by 5 min of stirring with anion-exchange resin renders a multi-gigabecquerel-level preparation of (131)I-IMP-R4-hMN-14 safe, convenient, and practical. 相似文献
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97.
Whipple TJ Le BH Demers LM Chinchilli VM Petit MA Sharkey N Williams NI 《International journal of sports medicine》2004,25(7):496-501
Resistance exercise has positive effects on bone mass, but little is known about the mechanisms by which this occurs. The purpose of this study was to determine if a single bout of moderate intensity resistance exercise alters biochemical markers of bone cell activity. Indices of bone turnover were measured in nine healthy, untrained men (21.9 +/- 1.2 yrs old), before and following a single 45 minute session of resistance exercise, and during a control trial. A cross-over design was used so that all participants performed both trials in random order. Blood samples were collected immediately before, immediately after, and at 1, 8, 24, and 48 hours post exercise and analyzed for bone-specific alkaline phosphatase (BAP), type I collagen propeptide (PICP), and type I collagen N-telopeptide (sNTX). Urine from the second morning void was collected over four days (day before, day of, and two days following exercise) and analyzed for type I collagen N-telopeptide (uNTX). Exercise resulted in a significant increase (p < 0.05) in the ratio of biochemical markers of bone formation to bone resorption eight hours post exercise, largely due to a decrease in sNTX. Markers return to baseline within 24 hrs. These data suggest that moderate intensity resistance training acutely reduces bone resorption, leading to a favorable change in overall bone turnover, for at least 8 hours post exercise in untrained young men. Further work is needed to determine if long-term benefits to bone strength follow with persistent training. 相似文献
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99.
Sharkey PF Shastri S Teloken MA Parvizi J Hozack WJ Rothman RH 《The Journal of arthroplasty》2004,19(6):694-699
This retrospective study explored the relationship between the volume of total hip arthroplasties (THA) and postoperative mortality and early complications from a single institution. One thousand hip arthroplasties in 932 patients were identified during a 1-year period, which included 786 primary and 214 revision hip arthroplasties. The postoperative 6-month combined medical and orthopedic complication rate for primary and revision THA was 7.9% and 16.5%, respectively. The 6-month mortality rate for the overall group was 0.5% (5 deaths), for the primary hips was 0.4% (3 deaths), and for the revision hip was 0.9% (2 deaths). The mortality and complication rates of many surgical procedures, including joint arthroplasties, are inversely related to hospital and surgical volume. The reduction in complication rate, however, approaches a plateau and does not improve regardless of an increase in the surgical and hospital volume. 相似文献
100.
The effect of ankle injury on subtalar motion 总被引:1,自引:0,他引:1
Michelson J Hamel A Buczek F Sharkey N 《Foot & ankle international / American Orthopaedic Foot and Ankle Society [and] Swiss Foot and Ankle Society》2004,25(9):639-646
BACKGROUND: Injuries to the medial and lateral ankle ligaments have been implicated in subtalar joint instability. Lateral injury increased subtalar joint varus and anterior translation, while deltoid injury increased external rotation and valgus in studies using static, non-physiologic testing. METHODS: The current study employed a physiologically accurate ankle model using phasic force-couples attached to the muscle-tendon units to reproduce ankle motion. Six-degree-of-freedom kinematics of the tibia, talus, and calcaneus were measured using a VICON motion analysis system under the following experimental conditions: 1) intact ligaments 2) complete lateral ligament injury with subsequent repair, 3) superficial deltoid injury with subsequent repair, and 4) deep deltoid injury without repair in eight harvested lower extremities. Statistical analysis was by repeated measures analyses of variance. RESULTS: At heel-strike, the subtalar joint is in internal rotation, dorsiflexion, and varus. As the leg progresses to foot-flat, there is external rotation, plantarflexion, and valgus rotation. From foot-flat to heel-rise, there is little subtalar joint motion, while at toe-off, there is slight internal rotation, dorsiflexion, and varus rotation. The total rotations amounted to 9.0 degrees (SD 5.0 degrees) external rotation, 6.1 degrees (SD 2.5 degrees) plantarflexion, and 7.8 degrees (SD 5.5 degrees) valgus. Disruption of the superficial deltoid increased plantarflexion (p < .001) and valgus (p < .05). The additional lateral injury increased both external rotation (p < .001) and valgus (p < .02). Lateral injury alone had no significant effect on subtalar joint motion. CONCLUSION: Unlike most previous reports, this study showed no significant influence of isolated lateral ankle injury on subtalar joint motion, probably because the current study examined subtalar joint motion under physiologic loading and motion rather than by static stress testing. This calls into question the relevance of static stress testing to the in situ function of the subtalar joint. The increased external rotation and valgus seen with deltoid injury in the current study is consistent with previous reports. 相似文献