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81.
Human cerebral acetylcholinesterase activity measured with positron emission tomography: procedure, normal values and effect of age 总被引:1,自引:0,他引:1
Hiroki Namba Masaomi Iyo Kiyoshi Fukushi Hitoshi Shinotoh Shin-ichiro Nagatsuka Tetsuya Suhara Yasuhiko Sudo Kazutoshi Suzuki Toshiaki Irie 《European journal of nuclear medicine and molecular imaging》1999,26(2):135-143
The regional cerebral metabolic rate of [11C]N-methyl-4-piperidyl acetate, which is nearly proportional to regional cerebral acetylcholinesterase (AChE) activity, was measured
by dynamic positron emission tomography in 20 healthy subjects with a wide age range (24–89 years). Quantitative measurement
was achieved using a kinetic model which consisted of arterial plasma and cerebral tissue compartments. The plasma input function
was obtained using thin-layer chromatography and an imaging phosphor plate system at frequent sampling intervals to catch
the rapid metabolism of the tracer in the blood. The distribution of the rate constant k
3, an index of AChE activity, agreed well with reported post-mortem AChE distribution in the cerebral cortex (0.067–0.097 min–1) and thalamus (0.268 min–1), where AChE activity was low to moderate. The k
3 values in the striatum and cerebellum, where AChE activity was very high, did not respond linearly to AChE activity because
of increased flow dependency. No significant effect of age was found on AChE activity of the cerebral cortex, suggesting that
the ascending central cholinergic system is preserved in normal aging. This study has shown that quantitative measurement
of enzyme activity in the living brain is possible through appropriate modelling of tracer kinetics and accurate measurement
of the input function. The method should be applicable to patients with Alzheimer’s disease and those with other kinds of
dementia whose central cholinergic system has been reported to be disturbed.
Received 2 June and in revised form 26 September 1998 相似文献
82.
Yukihiko Shirayama Kenji Hashimoto Hideyuki Matsuki Ko-ichi Tsunashima Masaomi Iyo Teruhiko Higuchi Yoshio Minabe 《Brain research》1999,839(1):16-185
Phencyclidine (PCP) has been shown to cause neurotoxicity in rat retrosplenial cortex following a single administration, although the precise mechanism underlying PCP-induced neurotoxicity is unclear. Using in situ hybridization and immunohistochemistry, we studied the effects of PCP on expression of immediate early gene zif268 mRNA and zif268 protein in the rat brain. High constitutive levels of zif268 mRNA and zif268 immunoreactivity were observed in the brain of control rats. Administration of PCP (12.5, 25 or 50 mg/kg, i.p., 6 h) caused marked induction of zif268 mRNA in the rat retrosplenial cortex, in a dose-dependent manner. However, the basal levels of zif268 mRNA in the other regions of cerebral cortex were decreased by administration of PCP. Emulsion-autoradiographical study suggested that marked expression of zif268 mRNA was observed in the layers III and IV of retrosplenial cortex where the neurotoxicity of PCP was detected. Furthermore, zif268 immunoreactivity in the layer IV of retrosplenial cortex was not changed by administration of PCP (25 mg/kg, i.p., 5 h), but that in the other layers of retrosplenial cortex was reduced by PCP. These results suggest that immediate early gene zif268 may, in part, play a role in the neurotoxicity of NMDA receptor antagonists such as PCP. 相似文献
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85.
IL-1 is required for allergen-specific Th2 cell activation and the development of airway hypersensitivity response 总被引:1,自引:0,他引:1
Nakae S Komiyama Y Yokoyama H Nambu A Umeda M Iwase M Homma I Sudo K Horai R Asano M Iwakura Y 《International immunology》2003,15(4):483-490
IL-1 is a pro-inflammatory cytokine consisted of two molecular species, IL-1alpha and IL-1beta, and the IL-1 receptor antagonist (IL-1Ra) is a natural inhibitor of both molecules. Although it is suggested that IL-1 potentiates immune responses mediated by T(h)2 cells, the role of IL-1 in asthma still remains unclear. In this study, we demonstrate that the ovalbumin (OVA)-induced airway hypersensitivity response (AHR) in IL-1alpha/beta-deficient (IL-1alpha/beta(-/-)) mice was significantly reduced from the levels seen in wild-type mice, whereas the responses seen in IL-1Ra(-/-) mice were profoundly exacerbated, suggesting that IL-1 is required for T(h)2 cell activation during AHR. OVA-specific T cell proliferation, IL-4 and IL-5 production by T cells, and IgG1 and IgE production by B cells in IL-1alpha/beta(-/-) mice were markedly reduced compared with these responses in wild-type mice; such responses were enhanced in IL-1Ra(-/-) mice. Using IL-1alpha(-/-) and IL-1beta(-/-) mice, we determined that both IL-1alpha and IL-1beta are involved in this reaction. Both IgG1 and IgE levels were reduced in IL-1beta(-/-) mice, while only IgE levels were affected in IL-1alpha(-/-) mice, indicating a functional difference between IL-1alpha and IL-1beta. These observations indicate that IL-1 plays important roles in the development of AHR. 相似文献
86.
Morita Y Ujike H Tanaka Y Uchida N Nomura A Ohtani K Kishimoto M Morio A Imamura T Sakai A Inada T Harano M Komiyama T Yamada M Sekine Y Iwata N Iyo M Sora I Ozaki N Kuroda S 《Neuroscience letters》2005,376(3):182-187
Genetic contributions to the etiology of substance abuse and dependence are topics of major interest. Acute and chronic cannabis use can produce drug-induced psychosis resembling schizophrenia and worsen positive symptoms of schizophrenia. The endocannabinoid system is one of the most important neural signaling pathways implicated in substance abuse and dependence. The fatty acid amide hydrolase (FAAH) is a primary catabolic enzyme of endocannabinoids. To clarify a possible involvement of FAAH in the etiology of methamphetamine dependence/psychosis or schizophrenia, we examined the genetic association of a nonsynonymous polymorphism of the FAAH gene (Pro129Thr) by a case-control study. We found no significant association in allele and genotype frequencies of the polymorphism with either disorder. Because the Pro129Thr polymorphism reduces enzyme instability, it is unlikely that dysfunction of FAAH and enhanced endocannabinoid system induce susceptibility to either methamphetamine dependence/psychosis or schizophrenia. 相似文献
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89.
Impact of end‐stage renal disease on hospital outcomes among patients admitted to intensive care units: A retrospective matched‐pair cohort study 下载免费PDF全文
90.
Hiromichi Ishiyama Takefumi Satoh Masashi Kitano Ken-ichi Tabata Shouko Komori Masaomi Ikeda Itaru Soda Shinji Kurosaka Akane Sekiguchi Masaki Kimura Shogo Kawakami Masatsugu Iwamura Kazushige Hayakawa 《Journal of radiation research》2014,55(3):509-517
The purpose of this study was to report the outcomes of high-dose-rate (HDR) brachytherapy and hypofractionated external beam radiotherapy (EBRT) combined with long-term androgen deprivation therapy (ADT) for National Comprehensive Cancer Network (NCCN) criteria-defined high-risk (HR) and very high-risk (VHR) prostate cancer. Data from 178 HR (n = 96, 54%) and VHR (n = 82, 46%) prostate cancer patients who underwent 192Ir-HDR brachytherapy and hypofractionated EBRT with long-term ADT between 2003 and 2008 were retrospectively analyzed. The mean dose to 90% of the planning target volume was 6.3 Gy/fraction of HDR brachytherapy. After five fractions of HDR treatment, EBRT with 10 fractions of 3 Gy was administered. All patients initially underwent ≥6 months of neoadjuvant ADT, and adjuvant ADT was continued for 36 months after EBRT. The median follow-up was 61 months (range, 25–94 months) from the start of radiotherapy. The 5-year biochemical non-evidence of disease, freedom from clinical failure and overall survival rates were 90.6% (HR, 97.8%; VHR, 81.9%), 95.2% (HR, 97.7%; VHR, 92.1%), and 96.9% (HR, 100%; VHR, 93.3%), respectively. The highest Radiation Therapy Oncology Group-defined late genitourinary toxicities were Grade 2 in 7.3% of patients and Grade 3 in 9.6%. The highest late gastrointestinal toxicities were Grade 2 in 2.8% of patients and Grade 3 in 0%. Although the 5-year outcome of this tri-modality approach seems favorable, further follow-up is necessary to validate clinical and survival advantages of this intensive approach compared with the standard EBRT approach. 相似文献