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61.
62.
The cytoskeleton in Chediak-Higashi syndrome fibroblasts 总被引:2,自引:0,他引:2
The Chediak-Higashi syndrome (CHS) trait is expressed in cultured human skin fibroblasts as an abnormal perinuclear concentration of moderately enlarged lysosomes. The cytoskeleton of CHS fibroblasts appears intact. Microtubules are normal in number and morphology, as assessed by colchicine binding studies, antitubulin immunofluorescence, and electron microscopy. Deformability by shear force is unaltered and microfilaments are abundant. However, CHS lysosomes appear to interact abnormally with the cytoskeleton, since the perinculear aggregation partially disperses after depolymerization of cell microtubules with colchicine. These results suggest that CHS is associated with a defect of either the lysosomal membrane itself or of lysosomal membrane- microtubule interaction. 相似文献
63.
The contribution of von Willebrand factor (vWF)-platelet binding to platelet-collagen interaction was examined in vitro. The binding of vWF to platelets was mediated and regulated by ristocetin. Subthreshold concentrations of ristocetin (less than or equal to 1 mg/mL), insufficient to cause ristocetin-induced platelet aggregation (RIPA), were added to platelet-rich plasma (PRP) prior to the addition of collagen. The collagen-induced platelet aggregation (CIPA) was modified by ristocetin and the degree of alteration was dependent on the ristocetin concentration. Response as a function of ristocetin concentration was designated the Collagen-Platelet Aggregation Response (CoI-PAR). In normal PRP the CoI-PAR was a progressive inhibition followed by decreasing inhibition and then an enhanced response. The enhanced response occurred over a narrow range of ristocetin concentrations (0.8 to 1.0 mg/mL). In the absence of vWF (severe von Willebrand's disease, Type I, vWF less than 1%) the CoI-PAR was a progressive, eventually complete inhibition with no enhanced response (with ristocetin concentrations up to 3.0 mg/mL). With addition of vWF to this PRP an enhanced response was observed at a ristocetin concentration inversely proportional to the vWF level. PRP from a patient with severe Hemophilia A showed a response within the normal range. Subthreshold ristocetin did not cause plasma protein precipitation or platelet release of 3H-serotonin, nor induce micro platelet aggregate formation. Digestion of platelet membrane glycoproteins (GP(s] with chymotrypsin demonstrated that upon removal of GPI, RIPA was absent, CIPA retained and the CoI-PAR was progressive inhibition, with no enhancement. With removal of GPs I, II, and III, RIPA, CIPA, and the CoI-PAR were absent. A dose-response 125I-vWF- platelet binding occurred with increasing ristocetin concentrations which was unchanged by the addition of collagen. These results demonstrated that ristocetin-platelet association inhibited CIPA, and vWF-platelet binding enhanced platelet-collagen adhesion and platelet aggregation. The in vitro-enhanced CIPA represents a vWF-dependent aggregation of sufficient magnitude to overcome the inhibitory effect of ristocetin. These studies demonstrate an influential interaction of ristocetin, vWF, and collagen with the platelet membrane and imply an important hemostatic contribution of vWF-platelet binding in platelet- collagen interaction. 相似文献
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65.
Li Tang Xujuan Yang Qian Yin Kaimin Cai Hua Wang Isthier Chaudhury Catherine Yao Qin Zhou Mincheol Kwon James A. Hartman Iwona T. Dobrucki Lawrence W. Dobrucki Luke B. Borst Stéphane Lezmi William G. Helferich Andrew L. Ferguson Timothy M. Fan Jianjun Cheng 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(43):15344-15349
Nanomedicines (NMs) offer new solutions for cancer diagnosis and therapy. However, extension of progression-free interval and overall survival time achieved by Food and Drug Administration-approved NMs remain modest. To develop next generation NMs to achieve superior anticancer activities, it is crucial to investigate and understand the correlation between the physicochemical properties of NMs (particle size in particular) and their interactions with biological systems to establish criteria for NM optimization. Here, we systematically evaluated the size-dependent biological profiles of three monodisperse drug–silica nanoconjugates (NCs; 20, 50, and 200 nm) through both experiments and mathematical modeling and aimed to identify the optimal size for the most effective anticancer drug delivery. Among the three NCs investigated, the 50-nm NC shows the highest tumor tissue retention integrated over time, which is the collective outcome of deep tumor tissue penetration and efficient cancer cell internalization as well as slow tumor clearance, and thus, the highest efficacy against both primary and metastatic tumors in vivo.Over the last two to three decades, consensus has been reached that the size of anticancer nanomedicines (NMs) plays a pivotal role in determining their biodistribution, tumor penetration, cellular internalization, and clearance from blood plasma and tissues as well as excretion from body, and thus, it has significant impact on overall therapeutic efficacy against cancers (1–7). Although most clinically approved anticancer NMs have size ranging from 100 to 200 nm (8, 9), recent studies showed that anticancer NMs with smaller sizes exhibited enhanced performance in vivo, such as greater tissue penetration and enhanced tumor inhibition, particularly those with size around or smaller than 50 nm (5–7, 10–12). As such, there has been a major push recently in the field of anticancer NM to miniaturize nanoparticle (NP) size using novel chemistry and engineering design (13–17). One unanswered question, however, is whether additional miniaturization of NM size would be necessary and result in additional improved anticancer efficacy. Widely evaluated small molecular therapeutics (<1,500 Da and <2 nm) can traverse most tumor tissues freely (18). However, they diffuse away from tumor tissues rapidly and get cleared primarily into tumor blood capillaries, leading to minimal tumor accumulation (18). Macromolecules of relatively low molecular masses (<40,000 Da and <10 nm) were also shown to have low overall tumor retention because of both rapid permeation into and clearance from tumor tissues, behaving to some extent like small molecule drugs (18, 19). In conjunction with the renal clearance threshold (<10–15 nm) (20, 21) and interstitial/lymphatic fenestration (<20 nm) (22) for NPs, it becomes essential to carefully and comprehensively evaluate the in vivo behavior and anticancer efficacy of NMs in the size range of 20–50 nm to determine the optimal size of NM for cancer therapy.In this study, we used monodisperse drug–silica nanoconjugates (NCs) that have identical physiochemical properties, except for size, to investigate the size-dependent biodistribution and tumor tissue penetration and clearance as well as the overall efficacy. We focused on the NCs of 20 and 50 nm in this particularly interesting size range as well as the NC of 200 nm, the upper size limit of systemic NM to extravasate leaky tumor vasculature, which has a cutoff pore size larger than 200 nm for most tumors (23). Among these three representative sizes, the 50-nm NC showed the optimal balance of deep tissue penetration and high retention in tumors, which is in contrast with its larger counterpart (the 200-nm NC) of limited tumor tissue penetration and smaller counterpart (the 20-nm NC) of fast clearance from tumors, leading to overall low tumor retention for both. Therefore, 50 nm could be or could be close to the optimal size of NCs in the studied size range of 20–200 nm, ensuring not only the efficient distribution in, but also the protracted availability of drug-containing NC to the tumor tissues, resulting in superior anticancer efficacy against both primary and metastatic tumors. 相似文献
66.
Matthew Christopher Musielak Ranjodh Singh Elizabeth Hartman Joseph Bernstein 《International journal of surgery case reports》2014,5(6):339-341
INTRODUCTION
Thrombosis of the inferior vena cava (IVC) is governed by Virchow''s triad of stasis of blood flow, endothelial damage and hypercoagulability. Causes may be secondary to malignancy, congenital anomalies or other infrequent events such as external compression. We present a case of external compression of the IVC leading to extensive thrombus burden secondary to a benign hepatic cyst.PRESENTATION OF CASE
A 72 year old African American female presented to the emergency department with new onset shortness of breath, right lower extremity weakness and swelling. CT imaging demonstrated multiple hepatic cysts compressing the IVC, leading to extensive clot burden. Treatment with heparin drip was initiated without resolution of her symptoms. Transcatheter mechanical thrombectomy and tPA infusion was performed. After 24 h, swelling and weakness were nearly resolved. The patient was bridged to therapeutic low molecular weight heparin in preparation for surgery.DISCUSSION
Management of IVC thrombosis has typically been with a heparin drip and transition to oral anticoagulants. Thrombolysis has been shown to promote complete clot lysis more often than compared to standard anticoagulant therapy. In addition, venous patency was better maintained.CONCLUSION
We feel that the added benefit of short term effects of improved venous patency and long term benefits of less post thrombotic syndrome, catheter based tPA administration and mechanical thrombectomy for thrombus offers an adjuvant treatment in the setting of large clot burden refractory to standard treatment. 相似文献67.
68.
Matthew S. Simon Selin Somersan Harjot K. Singh Barry Hartman Brian L. Wickes Stephen G. Jenkins Thomas J. Walsh Audrey N. Schuetz 《Journal of clinical microbiology》2014,52(1):374-378
Rhodotorula is an emerging opportunistic fungal pathogen that is rarely reported to cause endocarditis. We describe a case involving a patient who developed endocarditis due to Rhodotorula mucilaginosa and Staphylococcus epidermidis, proven by culture and histopathology. The case illustrates the unique diagnostic and therapeutic challenges relevant to Rhodotorula spp. 相似文献
69.
Rita A. Marvelli Houston A. Hobbs Shuxian Li Nancy K. McCoppin Leslie L. Domier Glen L. Hartman Darin M. Eastburn 《Archives of virology》2014,159(2):349-352
Virulence and double-stranded RNA (dsRNA) profiles of 44 isolates of Fusarium virguliforme were compared. When grouped according to dsRNA profiles, isolates with large dsRNAs were significantly (P≤0.05) less virulent than isolates without dsRNAs. High-throughput sequence analysis of total RNA prepared from cultures with large dsRNAs identified two novel RNA viruses with genome sequences of approximately 9.3 kbp, which were named Fusarium virguliforme dsRNA mycovirus 1 and Fusarium virguliforme dsRNA mycovirus 2. The new viruses were most closely related to a group of unclassified viruses that included viruses of F. graminearum and Phlebiopsis gigantea and are related to members of the family Totiviridae. 相似文献
70.
Orla McBride Sarah Butter Jamie Murphy Mark Shevlin Todd K. Hartman Kate M. Bennett Thomas V. A. Stocks Alex Lloyd Ryan McKay Jilly GibsonMiller Liat Levita Liam Mason Anton P. Martinez Philip Hyland Frdrique Vallires Thanos Karatzias Carmen Valiente Carmelo Vazquez Richard P. Bentall 《International journal of methods in psychiatric research》2022,31(1)
ObjectivesThis paper outlines fieldwork procedures for Wave 4 of the COVID‐19 Psychological Research Consortium (C19PRC) Study in the UK during November–December 2020.MethodsRespondents provided data on socio‐political attitudes, beliefs, and behaviours, and mental health disorders (anxiety, depression, and posttraumatic stress). In Phase 1, adults (N = 2878) were reinvited to participate. At Phase 2, new recruitment: (i) replenished the longitudinal strand to account for attrition; and (ii) oversampled from the devolved UK nations to facilitate robust between‐country analyses for core study outcomes. Weights were calculated using a survey raking algorithm to ensure the longitudinal panel was representative of the baseline sample characteristics.ResultsIn Phase 1, 1796 adults were successfully recontacted and provided full interviews at Wave 4 (62.4% retention rate). In Phase 2, 292 new respondents were recruited to replenish the panel, as well as 1779 adults from Wales, Scotland, and Northern Ireland, who were representative of the socio‐political composition of the adult populations in these nations. The raking procedure successfully re‐balanced the longitudinal panel to within 1% of population estimates for selected socio‐demographic characteristics.ConclusionThe C19PRC Study offers a unique opportunity to facilitate and stimulate interdisciplinary research addressing important public health questions relating to the COVID‐19 pandemic. 相似文献