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71.
Correlation between the effector functions and virus-neutralizing activity of antiviral immuno-globulin G (IgG) antibodies was investigated in relation to rabbit IgG antibodies against A/PR8/34 influenza virus. Changes in the effector activity of the antiviral antibodies were produced by reducing the single disulfide bond between the heavy chains in the hinge region of the IgG molecule. Antiinfluenzal IgG, when reduced in this way, retained about 50% of its complement-fixing activity but lost virtually all its ability to be bound to heterologous tissues. Meanwhile the reduced antiinfluenzal IgG, as the results of the delayed hemagglutination test showed, completely preserved its antigen-binding activity. The virus-neutralizing activity of the reduced antiinfluenzal IgG, as estimated in experiments on chick embryos, was indistinguishable from the activity of the native preparation if the dose of virus used in the experiments was 100 EID50. If the dose of virus was increased to 1000 EID50 the virus-neutralizing activity of the reduced IgG was less than that of the native preparation. The results are discussed in terms of differences in the structural organization of reduced IgG.N. F. Gamaleya Institute of Epidemiology and Microbiology, Moscow. D. I. Ivanovskii Institute of Virology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 8, pp. 188–191, August, 1977.  相似文献   
72.
Patients with end-stage renal disease (ESRD) exhibit immune dysregulation, but the precise immunological profile and the effect of hemodialysis (HD) on it has not been investigated fully. Thirty-eight ESRD patients (22 on HD and 16 in pre-dialysis) and 24 healthy volunteers were included. We compared the T cell immune profiles as in these patients. Among the effector T cell subset, the percentages of Th17 and Th2 cells were significantly higher in the ESRD group than in the healthy controls (P<0.05). The percentage of Th1 cells did not differ significantly between these groups. The percentages of Th1, Th2 and Th17 cells did not differ significantly (P>0.05) between the two subgroups within the ESRD group. The CCR4(-)CCR6(+)/CD4(+) T cell percentage was also significantly higher in the ESRD group. The na?ve T cell (T(na?ve)) percentage was significantly lower in the ESRD group, and the difference between patients and controls was greater in the pre-dialysis patients than in the HD patients (P<0.05, for each comparison). By contrast, the percentages of central memory T cells (T(CM)) and effector memory T (T(EM)) cells were significantly higher in the ESRD group. Interleukin-17 production by T(EM) cells was significantly higher in the ESRD group. The severity of uremia was related negatively to the T(na?ve) cell percentage but positively to the T(CM) and T(EM) cell percentages. The percentages of T(EM) and CD45RA(+) T effector memory subsets of CD8(+) T cells were significantly higher in the ESRD group (P<0.05). The result of this study showed significantly altered T cell-associated immunity and that it could not be corrected with hemodialysis.  相似文献   
73.
目的 观察膏摩法结合超声药物透入治疗颈源性肩背痛的疗效及相关效应因子的调节变化。方法 随机将符合要求的96例颈源性肩背痛患者分为两组,治疗组48例,对照组48例。治疗组以膏摩手法结合超声药物透入疗法,对照组采用常规手法结合口服塞来昔布胶囊的方法。分别观察两组治疗前后的疗效及相关效应(炎性)因子白细胞介素-1β受体拮抗剂、白细胞介素-6及肿瘤坏死因子的浓度变化,并参照标准进行临床疗效的评定。结果 两组的炎性因子浓度变化方面:治疗后血清白细胞介素-1β受体拮抗剂浓度均增加,治疗组增加程度大于对照组(t=4.157,P=0.0001),两组血清白细胞介素-6浓度均有降低,治疗组降低程度大于对照组(t=8.739,P=0.0001),两组血清肿瘤坏死因子浓度均有降低,治疗组降低程度大于对照组(t=2.727,P=0.0076);临床疗效方面:治疗组总有效率91.7%,对照组总有效率75.0%,疗效优于对照组(F=0.026)。结论 膏摩法结合超声药物透入治疗颈源性肩背痛的疗效优于常规手法及服药,能调节血清中白细胞介素-1β受体拮抗剂、白细胞介素-6和肿瘤坏死因子等的浓度,是治疗颈源性肩背痛较为有效的方法。  相似文献   
74.
Aggregation of alpha-synuclein may contribute to neuropathology in Parkinson's disease patients and in transgenic animal models. Natively unfolded alpha-synuclein binds to various proteins and conformational changes due to alpha-synuclein misfolding may alter physiological interactions. In the present study, we used protein arrays spotted with 5000 recombinant human proteins for a large scale interaction analysis of monomeric versus oligomeric alpha-synuclein. Monomeric alpha-synuclein bound to arrayed cAMP regulated phosphoprotein 19 and binding appears to be disrupted by alpha-synuclein oligomerization. Incubation with recombinant alpha-synuclein oligomers lead to the identification of several GTPase activating proteins and Cdc42 effector proteins as binding partners. Protein database searches revealed a Cdc42/Rac interactive binding domain in some interactors. To demonstrate in vivo relevance, we analyzed brainstem protein extracts from alpha-synuclein(A30P) transgenic mice. Pull-down assays using beads conjugated with a Cdc42/Rac interactive binding domain lead to an enrichment of endogenous alpha-synuclein oligomers. Cdc42 effector proteins were also co-immunoprecipitated with alpha-synuclein from brainstem lysates and were colocalized with alpha-synuclein aggregates in brain sections by double immunostaining. By two-dimensional gel electrophoretic analysis of synaptosomal fractions from transgenic mouse brains we detected additional isoforms of septin 6, a downstream target of Cdc42 effector proteins. Small GTPases have recently been identified in a genetic modifier screen to suppress alpha-synuclein toxicity in yeast. Our data indicate that components of small GTPase signal transduction pathways may be directly targeted by alpha-synuclein oligomers which potentially leads to signaling deficits and neurodegeneration.  相似文献   
75.
76.
SifA is a bi-functional Type III Secretion System (T3SS) effector protein that plays an important role in Salmonella virulence. The N-terminal domain of SifA binds SifA-Kinesin-Interacting-Protein (SKIP), and via an interaction with kinesin, forms tubular membrane extensions called Sif filaments (Sifs) that emanate from the Salmonella Containing Vacuole (SCV). The C-terminal domain of SifA harbors a WxxxE motif that functions to mimic active host cell GTPases. Taken together, SifA functions in inducing endosomal tubulation in order to maintain the integrity of the SCV and promote bacterial dissemination. Since SifA performs multiple, unrelated functions, the objective of this study was to determine how each functional domain of SifA becomes processed. Our work demonstrates that a linker region containing a caspase-3 cleavage motif separates the two functional domains of SifA. To test the hypothesis that processing of SifA by caspase-3 at this particular site is required for function and proper localization of the effector protein domains, we developed two tracking methods to analyze the intracellular localization of SifA. We first adapted a fluorescent tag called phiLOV that allowed for type-III secretion system (T3SS) mediated delivery of SifA and observation of its intracellular colocalization with caspase-3. Additionally, we created a dual-tagging strategy that permitted tracking of each of the SifA functional domains following caspase-3 cleavage to different subcellular locations. The results of this study reveal that caspase-3 cleavage of SifA is required for the proper localization of functional domains and bacterial dissemination. Considering the importance of these events in Salmonella pathogenesis, we conclude that caspase-3 cleavage of effector proteins is a more broadly applicable effector processing mechanism utilized by Salmonella to invade and persist during infection.  相似文献   
77.
Isolated peripheral blood CD4 cells from allergic individuals express CC chemokine receptor (CCR)3 and CCR4 after expansion in vitro. In addition, human T helper type 2 (Th2) cells polarized in vitro selectively express CCR3 and CCR4 at certain stages of activation/differentiation and respond preferentially to the ligands eotaxin and monocyte-derived chemokine (MDC). However, controversy arises when the in vivo significance of this distinct expression is discussed. To address the functional role of CCR3/eotaxin and CCR4/MDC during the in vivo recruitment of Th2 cells, we have transferred effector Th cells into naive mice to induce allergic airway disease. Tracking of these cells after repeated antigen challenge has established that both CCR3/eotaxin and CCR4/MDC axes contribute to the recruitment of Th2 cells to the lung, demonstrating the in vivo relevance of the expression of these receptors on Th2 cells. We have shown that involvement of the CCR3/eotaxin pathway is confined to early stages of the response in vivo, whereas repeated antigen stimulation results in the predominant use of the CCR4/MDC pathway. We propose that effector Th2 cells respond to both CCR3/eotaxin and CCR4/MDC pathways initially, but that a progressive increase in CCR4-positive cells results in the predominance of the CCR4/MDC axis in the long-term recruitment of Th2 cells in vivo.  相似文献   
78.
It has been 35 y since Carl Woese reported in PNAS how sequencing ribosomal RNA genes could be used to distinguish the three domains of life on Earth. During the past decade, 16S rDNA sequencing has enabled the now frequent enumeration of bacterial communities that populate the bodies of humans representing different ages, cultural traditions, and health states. A challenge going forward is to quantify the contributions of community members to wellness, disease risk, and disease pathogenesis. Here, we explore a theoretical framework for studies of the inheritance of bacterial strains and discuss the advantages and disadvantages of various study designs for assessing the contribution of strains to complex diseases.  相似文献   
79.
80.
The bacterial pathogen Vibrio parahaemolyticus utilizes a type III secretion system to cause death of host cells within hours of infection. We report that cell death is completely independent of apoptosis and occurs by a mechanism in which injection of multiple type III effectors causes induction of autophagy, cell rounding, and the subsequent release of cellular contents. Autophagy is detected by the appearance of lipidated light chain 3 (LC3) and by increases in punctae and vacuole formation. Electron microscopy reveals the production of early autophagic vesicles during infection. Consistent with phosphoinositide 3 (PI3) kinase playing a role in autophagy, treatment of infected cells with a PI3 kinase inhibitor attenuates autophagy in infected cells. Because many effectors are injected during a V. parahaemolyticus infection, it is not surprising that the presence of a sole PI3 kinase inhibitor does not prevent inevitable host-cell death. Our studies reveal an infection paradigm whereby an extracellular pathogen uses its type III secretion system to cause at least three parallel events that eventually result in the proinflammatory death of an infected host cell.  相似文献   
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