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排序方式: 共有284条查询结果,搜索用时 15 毫秒
41.
SNAP-25 deficit and hippocampal connectivity in schizophrenia 总被引:3,自引:2,他引:1
Young CE; Arima K; Xie J; Hu L; Beach TG; Falkai P; Honer WG 《Cerebral cortex (New York, N.Y. : 1991)》1998,8(3):261-268
Regional abnormalities of brain connectivity may be an important substrate
for the expression of schizophrenia, a severe form of mental illness. Brain
imaging and postmortem morphometric studies indicate hippocampal structure
is abnormal in schizophrenia. To study molecular components of hippocampal
connectivity the presynaptic proteins SNAP-25 and synaptophysin were
assayed in postmortem samples. Immunocytochemical studies indicated reduced
SNAP-25 immunoreactivity in schizophrenia compared to controls,
particularly in the terminal fields of entorhinal cortex projections.
Although there were no overall changes in synaptophysin immunoreactivity,
in the granule cell layer of the dentate gyrus synaptophysin
immunoreactivity was increased in schizophrenia. These results indicate
that disconnection of a subset of hippocampal circuitry from the entorhinal
cortex, as well as intrinsic changes in hippocampal connectivity, may
contribute to the mechanism of illness in schizophrenia.
相似文献
42.
Fleischman AG Aichberger KJ Luty SB Bumm TG Petersen CL Doratotaj S Vasudevan KB LaTocha DH Yang F Press RD Loriaux MM Pahl HL Silver RT Agarwal A O'Hare T Druker BJ Bagby GC Deininger MW 《Blood》2011,118(24):6392-6398
Proinflammatory cytokines such as TNFα are elevated in patients with myeloproliferative neoplasms (MPN), but their contribution to disease pathogenesis is unknown. Here we reveal a central role for TNFα in promoting clonal dominance of JAK2(V617F) expressing cells in MPN. We show that JAK2(V617F) kinase regulates TNFα expression in cell lines and primary MPN cells and TNFα expression is correlated with JAK2(V617F) allele burden. In clonogenic assays, normal controls show reduced colony formation in the presence of TNFα while colony formation by JAK2(V617F)-positive progenitor cells is resistant or stimulated by exposure to TNFα. Ectopic JAK2(V617F) expression confers TNFα resistance to normal murine progenitor cells and overcomes inherent TNFα hypersensitivity of Fanconi anemia complementation group C deficient progenitors. Lastly, absence of TNFα limits clonal expansion and attenuates disease in a murine model of JAK2(V617F)-positive MPN. Altogether our data are consistent with a model where JAK2(V617F) promotes clonal selection by conferring TNFα resistance to a preneoplastic TNFα sensitive cell, while simultaneously generating a TNFα-rich environment. Mutations that confer resistance to environmental stem cell stressors are a recognized mechanism of clonal selection and leukemogenesis in bone marrow failure syndromes and our data suggest that this mechanism is also critical to clonal selection in MPN. 相似文献
43.
Inhibition of calcineurin phosphatase activity in adult bone marrow transplant patients treated with cyclosporine A 总被引:1,自引:1,他引:1
Pai SY; Fruman DA; Leong T; Neuberg D; Rosano TG; McGarigle C; Antin JH; Bierer BE 《Blood》1994,84(11):3974-3979
In vitro studies have demonstrated that cyclosporine A (CsA) acts by inhibiting the phosphatase activity of calcineurin, an important mediator of T-cell activation. The relationship of CsA administration in vivo, calcineurin activity, and graft-versus-host disease (GVHD) has yet to be studied. The calcineurin activities of mononuclear cells isolated from 62 bone marrow transplant recipients and 12 normal volunteers were determined and analyzed with respect to administration of CsA, presence or absence of CsA in plasma, and presence or absence of GVHD. Of 62 patients, 33 were taking CsA and 29 were not. Early posttransplant (< 100 days), the calcineurin activity of patients on CsA was significantly lower than that of patients not on CsA (P = .0004) and than that of normal volunteers (P < .0001). Similarly, late posttransplant (> 100 days), the calcineurin activity of patients taking CsA was inhibited compared with normal volunteers (P < .05). The calcineurin activity of patients with acute GVHD who were taking CsA was lower than that of patients on CsA without acute GVHD matched for time posttransplant (P = .02). Calcineurin activity in patients on CsA with chronic GVHD was similar to those without chronic GVHD on drug. In conclusion, calcineurin activity is significantly suppressed by in vivo administration of CsA. The lower calcineurin activity of patients on CsA with acute GVHD suggests that CsA-resistant GVHD is not the result of inadequate suppression of calcineurin activity. These data suggest that if inhibition of calcineurin is the only physiologic target of CsA administration, simply increasing doses of CsA or treatment with other inhibitors of calcineurin, such as FK506, would not be expected to ameliorate GVHD. 相似文献
44.
Pavel Drevinek Matthew TG Holden Zhaoping Ge Andrew M Jones Ian Ketchell Ryan T Gill Eshwar Mahenthiralingam 《BMC infectious diseases》2008,8(1):1-16
Background
Effective prophylaxis and treatment for infections caused by biological threat agents (BTA) rely upon early diagnosis and rapid initiation of therapy. Most methods for identifying pathogens in body fluids and tissues require that the pathogen proliferate to detectable and dangerous levels, thereby delaying diagnosis and treatment, especially during the prelatent stages when symptoms for most BTA are indistinguishable flu-like signs.Methods
To detect exposures to the various pathogens more rapidly, especially during these early stages, we evaluated a suite of host responses to biological threat agents using global gene expression profiling on complementary DNA arrays.Results
We found that certain gene expression patterns were unique to each pathogen and that other gene changes occurred in response to multiple agents, perhaps relating to the eventual course of illness. Nonhuman primates were exposed to some pathogens and the in vitro and in vivo findings were compared. We found major gene expression changes at the earliest times tested post exposure to aerosolized B. anthracis spores and 30 min post exposure to a bacterial toxin.Conclusion
Host gene expression patterns have the potential to serve as diagnostic markers or predict the course of impending illness and may lead to new stage-appropriate therapeutic strategies to ameliorate the devastating effects of exposure to biothreat agents. 相似文献45.
46.
47.
Background
Soft tissue navigation has traditionally been neglected in computer-aided surgery (CAS) because of unpredictable margins of error. In our study, we examined clinical cases in which standard CAS was applied in soft tissue surgery in the head and neck region. Its extended applicability, margins of error, and general performance are described and discussed.Materials and methods
CAS was applied in surgical procedures for six patients. Five patients had foreign bodies in the head and neck region, and one patient displayed uncertain cervical lymph node enlargement. An optoelectrical navigation system (VectorVision2, BrainLAB) was used in all cases.Results
Using CAS, 10 out of 11 total foreign bodies were identified. Only one glass splinter attached to the eyeball could not be detected by the navigation system. One glass splinter that was deeply buried within the sphenoid bone was easily found but was left untouched. The parapharyngeal lymph node was identified and extracted in a minimally invasive transpalatinal approach.Conclusions
Soft tissue navigation was successfully applied in all but one case; the success was due to the altered demands in soft tissue navigation as opposed to skull-base surgery. Easy identification of foreign bodies and lymph nodes was possible in the soft tissues of the head and neck, with an acceptable margin of error. 相似文献48.
Studies on the origin of redox enzymes in seminal plasma and their relationship with results of in-vitro fertilization 总被引:3,自引:0,他引:3
Yeung CH; Cooper TG; De Geyter M; De Geyter C; Rolf C; Kamischke A; Nieschlag E 《Molecular human reproduction》1998,4(9):835-839
Glutathione (GSH), GSH peroxidase (GPX), GSH reductase (GRD), superoxide
dismutase (SOD) and catalase-like enzyme activity were quantified in
seminal plasma from normozoospermic patients, men with known distal ductal
occlusion, proven fathers and male partners of couples receiving in-vitro
fertilization (IVF) treatment for both male and female causes. Glutathione
was non-detectable (< 2.5 microM) in seminal plasma. None of the enzyme
activities per unit volume were lower in semen from vasectomized men,
suggesting that they did not originate substantially from the testis or
epididymis. The strongest relationships between enzyme activities and
accessory gland markers were between zinc and GRD (r = 0.678), SOD (r =
0.602) and GPX (r = 0.548), suggesting a largely prostatic origin of these
enzymes. Only weak relationships between accessory gland markers and
catalase-like activity suggested a multi-glandular source of this enzyme.
There was no relationship between the activity of any of the enzymes in the
IVF patients with their fertilization rates in vitro or the establishment
of pregnancy after IVF. Nor was there any correlation of enzyme activity
with the morphology and percentage of motile spermatozoa in semen or with
the percentage motility of spermatozoa immediately after swim-up or after
overnight incubation. These findings suggest that the protective enzymes in
the seminal plasma are contributed largely by the prostate and little by
the epididymis, and that in most cases of IVF, they have no major influence
on the outcome.
相似文献
49.
50.
This randomized double-blind placebo-controlled study was initiated to analyze the behavior of epididymis, processus vaginalis and testicular descent in cryptorchid boys treated with a low dose (20 g) of a luteinizing hormone-releasing hormone analogue (Buserelin), administered daily, as a nasal spray, for a short period (28 days). Fifty-nine true cryptorchid boys were randomly assigned to 3 groups: buserelin, treatment [22], surgical treatment [18] or placebo control group [19]. The 3 groups of patients were similar before treatment in regard to testicular position, chronological and bone age, height and weight, luteinizing hormone, follicle-stimulating hormone, testosterone, penile size and the volume of the contralateral descended testis. None of the patients had retractile testes. Buserelin significantly induced testicular descent compared to the boys treated with a placebo (P<0.01). A normal epididymis was found more often in boys with successful descent (P<0.003). A closed processus vaginalis was also more frequently observed in the group treated with buserelin than in surgically treated one (P<0.05). In conclusion, buserelin was capable of inducing testicular descent besides provoking further development of the epididymis and closing the processus vaginalis. 相似文献