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排序方式: 共有702条查询结果,搜索用时 31 毫秒
1.
ObjectivePrevious studies have shown that hydrogen sulfide (H2S) exerts potent proangiogenic properties under in vitro conditions and in rodent models. We sought to determine whether a novel H2S prodrug promotes peripheral revascularization in a swine model of acute limb ischemia (ALI).MethodsALI was induced in 17 female miniswine via intravascular occlusion of the external iliac. At day 7 after ALI induction, miniswine (n = 17) were randomized to received placebo or the H2S prodrug, SG-1002 (800 mg per os twice a day), for 35 days. At day 35 SG-1002 increased circulating levels of H2S (5.0 ± 1.2 μmol/L vs 1.8 ± 0.50 μmol/L; P < .05), sulfane sulfur (10.6 ± 2.3 μmol/L vs 2.6 ± 0.8 μmol/L; P < .05), and nitrite (0.5 ± 0.05 μmol/L vs 0.3 ± 0.03 μmol/L; P < .005) compared with placebo. SG-1002 therapy increased angiographic scoring in ischemic limb vessel number (27.6 ± 1.6 vs 22.2 ± 1.8; P < .05) compared with placebo. Treatment with SG-1002 preserved existing capillaries in ischemic limbs (128.3 ± 18.7 capillaries/mm2 vs 79.0 ± 9.8 capillaries/mm2; P < .05) compared with placebo. Interestingly, treatment with SG-1002 also improved coronary vasorelaxation responses to bradykinin and substance P in miniswine with ALI.ConclusionsOur results suggest that daily administration of the H2S prodrug, SG-1002, leads to an increase in circulating H2S and nitric oxide signaling and preserves vessel number and density in ischemic limbs. Furthermore, SG-1002 therapy improved endothelial-dependent coronary artery vasorelaxation in the setting of ALI. Our data demonstrate that SG-1002 preserves the vascular architecture in ischemic limbs and exerts vascular protective effects in the coronary vasculature in a model of peripheral vascular disease.  相似文献   
2.
《Vaccine》2022,40(19):2723-2732
Control of swine influenza A virus (swIAV) in North America and Europe is complicated because multiple antigenically distinct swIAV strains co-circulate in the field, and no vaccine is available that can provide broad cross-protection against all these swIAVs. In 2017, the first live attenuated influenza vaccine (LAIV) for swine was licensed in the US. The non-structural protein 1 (NS1)-truncated cluster I H3N2 strain A/swine/Texas/4199-2/98 NS1del126 (TX98 LAIV) in this vaccine provides partial cross-protection against heterologous North American cluster II and IV H3N2 swIAV strains. Its efficacy against European or more recent North American H3N2 lineages remains to be investigated. In this study, we evaluated the level of cross-protection against heterologous IAVs representative of the major H3N2 swIAV lineages in Europe and North America. TX98 LAIV prevented both nasal shedding and replication in the lungs of a North American cluster IV H3N2 swIAV for 2/4 pigs, prevented considerable nasal shedding of a North American novel human-like H3N2 swIAV for 2/4 pigs, and reduced replication of a European H3N2 swIAV in the lower respiratory tract to minimal titers for 1/3 pigs. Although TX98 LAIV elicited neutralizing antibodies against the homologous virus in serum and to a lesser extent in nose and lungs, no significant cross-reactive antibody titers against the heterologous swIAVs were detected. Partial cross-protection therefore likely relies on cellular and mucosal immune responses against conserved parts of the swIAV proteins. Since TX98 LAIV can offer partial protection against a broad range of H3N2 swIAVs, it might be a suitable priming vaccine for use in a heterologous prime-boost vaccination strategy.  相似文献   
3.
《Vaccine》2022,40(43):6255-6270
Swine influenza A virus (swIAV) infections in pig populations cause considerable morbidity and economic losses. Frequent reverse zoonotic incursions of human IAV boost reassortment opportunities with authentic porcine and avian-like IAV in swine herds potentially enhancing zoonotic and even pre-pandemic potential. Vaccination using adjuvanted inactivated full virus vaccines is frequently used in attempting control of swIAV infections. Accelerated antigenic drift of swIAV in large swine holdings and interference of maternal antibodies with vaccine in piglets can compromise these efforts. Potentially more efficacious modified live-attenuated vaccines (MLVs) bear the risk of reversion of MLV to virulence. Here we evaluated new MLV candidates based on cold-passaged swIAV or on reassortment-incompetent bat-IAV-swIAV chimeric viruses. Serial cold-passaging of various swIAV subtypes did not yield unambiguously temperature-sensitive mutants although safety studies in mice and pigs suggested some degree of attenuation. Chimeric bat-swIAV expressing the hemagglutinin and neuraminidase of an avian-like H1N1, in contrast, proved to be safe in mice and pigs, and a single nasal inoculation induced protective immunity against homologous challenge in pigs. Reassortant-incompetent chimeric bat-swIAV vaccines could aid in reducing the amount of swIAV circulating in pig populations, thereby increasing animal welfare, limiting economic losses and lowering the risk of zoonotic swIAV transmission.  相似文献   
4.
目的 探讨分离于广西猪流感病毒SW/Guangxi/NS2783/2010和SW/Guangxi/NS650/2012跨种属感染人肺腺癌A549细胞的miRNA93和miRNA192对病毒复制及宿主抗病毒免疫的影响。方法 通过测定不同稀释浓度的病毒感染细胞HA滴度值,确定病毒最佳稀释浓度。荧光定量PCR检测病毒感染细胞后miRNA93和miRNA192表达,Western blot检测病毒NP和HA蛋白表达水平;转染miRNA93和miRNA192抑制剂后,重新检测miRNA93、miRNA192、IFN-β及病毒NP、HA蛋白表达水平。结果 不同稀释度病毒感染人A549细胞后HA滴度的结果显示病毒SW2783的最佳稀释度为10-3,而SW650的HA滴度无明显变化趋势,提示病毒SW2783对人A549细胞具有较好的适应性和感染能力。荧光定量PCR和Western blot结果提示两株病毒感染细胞后病毒NP和HA蛋白表达均先升高后降低,加入miRNA93抑制剂,两株病毒NP和HA蛋白的表达均上调;加入miRNA192抑制剂,病毒SW2783的HA蛋白表达下调(P=2.10×10-4),而SW650的HA蛋白表达上调(P=5.45×10-5),NP蛋白反而下调(P=0.034);ELISA结果提示病毒SW2783和SW650感染细胞后炎症因子IFN-β表达水平随感染时间延长而升高。结论 研究表明miRNA93和miRNA192的表达与SIV病毒增殖及宿主抗病毒免疫有关,可作为干预猪流感病毒跨种属感染的新靶点。  相似文献   
5.
《Vaccine》2016,34(10):1241-1246
Swine are often asymptomatic carriers of Salmonella spp., a leading cause of human bacterial foodborne disease. Vaccination against Salmonella is effective for protecting animal health and enhancing food safety. However, with >2500 Salmonella serovars, current vaccines for swine offer limited cross-protection against heterologous serovars. Also, existing vaccines can interfere with surveillance programs that monitor the Salmonella status of swine herds. To overcome Salmonella vaccine limitations, we rationally designed and constructed an attenuated Salmonella enterica serovar Typhimurium vaccine (BBS 866) by deleting multiple small regulatory RNA (sRNA) genes (omrA, omrB, rybB, micA, and invR) in combination with an rfaH mutation. We vaccinated swine intranasally at 3-weeks of age with PBS (mock-vaccinated), BBS 866 or BBS 202 (S. Typhimurium rfaH, Bearson et al., Front Vet Sci 2014;1:9.) and challenged at 7-weeks of age with virulent S. Choleraesuis, a swine pathogen. Vaccination with BBS 866 enhanced protection against S. Choleraesuis by significantly limiting the duration of fever, weight loss, the levels of circulating INFγ, and the total number of swine with S. Choleraesuis septicemia. Vaccination with either BBS 866 or BBS 202 significantly reduced S. Choleraesuis colonization of both systemic (spleen and liver) and gastrointestinal (Peyer's Patch, Ileocecal lymph nodes, and cecum) tissues. Similar to our earlier report for BBS 202, the BBS 866 vaccine strain can be used in swine without compromising the differentiation of infected from vaccinated animals (DIVA). Therefore, the attenuated S. Typhimurium BBS 866 strain, containing mutations in rfaH and multiple sRNAs, addresses the limitations of current Salmonella vaccines by providing cross-protection against Salmonella serovars in swine without interfering with established monitoring programs for Salmonella surveillance.  相似文献   
6.
The area postrema (AP) is being widely studied to delineate its role in such varied functions as blood pressure regulation, conditioned taste aversion, water and energy balance, and radiation-induced emesis. This paper describes the preoperative preparation, surgical procedure, and postoperative care of cats kept long-term in which the AP was lesioned by electrocautery. A dorsal midline approach under gas anesthesia allowed access to selectively lesion the AP. Cats fully regained consciousness the same day and many became homeostutic within 24-48 h. Results of experiments using this model demonstrate the usefulness and effectiveness of the technique for model preparation.  相似文献   
7.

Background and purpose

Paralysis observed during a study of vertebral bone tolerance to single-session irradiation led to further study of the dose-related incidence of motor peripheral neuropathy.

Materials and methods

During a bone tolerance study, cervical spinal nerves of 15 minipigs received bilateral irradiation to levels C5–C8 distributed into three dose groups with mean maximum spinal nerve doses of 16.9 ± 0.3 Gy (n = 5), 18.7 ± 0.5 Gy (n = 5), and 24.3 ± 0.8 Gy (n = 5). Changes developing in the gait of the group of pigs receiving a mean maximum dose of 24.3 Gy after 10–15 weeks led to the irradiation of two additional animals. They received mean maximum dose of 24.9 ± 0.2 Gy (n = 2), targeted to the left spinal nerves of C5–C8. The followup period was one year. Histologic sections from spinal cords and available spinal nerves were evaluated. MR imaging was performed on pigs in the 24.9 Gy group.

Results

No pig that received a maximum spinal nerve point dose ?19.0 Gy experienced a change in gait while all pigs that received ?24.1 Gy experienced paralysis. Extensive degeneration and fibrosis were observed in irradiated spinal nerves of the 24.9 Gy animals. All spinal cord sections were normal. Irradiated spinal nerve regions showed increased thickness and hypointensity on MR imaging.

Conclusion

The single-session tolerance dose of the cervical spinal nerves lies between 19.0 and 24.1 Gy for this model.  相似文献   
8.
目的 观察以供体腹主动脉重建肝动脉对受体血流动力学和心肌肌钙蛋白Ⅰ(cTnI)的影响.方法 将健康广西巴马小型猪12头随机分为供、受体两组,每组6头,受体再随机分为A组(肝动脉吻合组)和B组(腹主动脉吻合组)),每组3头.供、受体动物均接受静脉全身麻醉,气管插管后行机械通气.供体动物行快速肝脏切取术取出供肝.受体动物置入Swan-Ganz导管,行背驮式肝移植术,A、B组采用不同的肝动脉重建方式,A组在不阻断腹主动脉下采用肝动脉端端连续吻合,B组在阻断腹主动脉后以其腹主动脉侧壁和供肝腹主动脉行端侧吻合.检测开腹前5 min (T0)、无肝期30min (T1)、新肝期30 min (T2)、肝动脉重建后10 min (T3)、术毕时(T4)、术后1 h(T5)6个时间点的平均动脉压(MAP)、心率(HR)、中心静脉压(CVP)、肺动脉压(PAP)、肺动脉楔压(PCWP)、心排量(C0)等血流动力学参数和cTnI.结果 在T0~T2时,组间各指标无差别;在T3时点,B组HR、CO低于A组,MAP、CVP、PAP、PCWP高于A组,cTnI组间无差别;在T4、T5时,B组MAP低于A组,CVP、PAP、PCWP、cTnI高于A组,HR、CO组间无差别.结论 采用完全阻断腹主动脉和以腹主动脉行端侧吻合的肝动脉重建方式加重了血流动力学的变化和心肌损伤.  相似文献   
9.
The diversity of contemporary swine influenza virus (SIV) strains impedes effective immunization of swine herds. Mucosally delivered, attenuated virus vaccines are one approach with potential to provide broad cross-protection. Reverse genetics-derived H3N2 SIV virus with truncated NS1 (NS1Δ126 TX98) is attenuated and immunogenic when delivered intranasally in young pigs. We analyzed T-cell priming and cross-protective efficacy in weanling piglets after intranasal inoculation with NS1Δ126 TX98 versus wild type TX98. In vivo replication of the truncation mutant was minimal compared to the wild type virus. T-cell responses were greater in magnitude in pigs infected with the wild type virus in in vitro restimulation assays. According to the expression of activation marker CD25, peripheral T cell recall responses in NS1Δ126 TX98 infected pigs were minimal. However, intracellular IFN-γ data indicate that the attenuated virus induced virus-specific CD4+CD8-, CD4+CD8+, CD4-CD8+, and γδ T cells within 28 days. The IFN-γ response appeared to contract, as responses were reduced at later time points prior to challenge. CD4+CD8+ cells isolated 5 days after heterosubtypic H1N1 challenge (day 70 overall) showed an elevated CD25 response to virus restimulation. Pigs previously infected with wild type TX98 were protected from replication of the H1N1 challenge virus. Vaccination with NS1Δ126 TX98 was associated with significantly lower levels of Th1-associated cytokines in infected lungs but provided partial cross-protection against the H1N1 challenge. These results demonstrate that NS1Δ SIV vaccines can elicit cell-mediated cross-protection against antigenically divergent strains.  相似文献   
10.

Objective

The herbal agent celandine is thought to have mainly spasmolytic effects, but in the uterus it is regarded as promoting contractions, which can offer promising and innovative options for optimizing artificial reproduction. The aim of the present study was to investigate the effect of celandine on the uterine muscle, using a perfusion model of swine uteri.

Study design

Sixteen swine uteri were perfused with Krebs–Ringer solution. Celandine (Chelidonium, Paverysat; Johannes Bürger Ysatfabrik Ltd., Bad Harzburg, Germany) was administered at increasing dosages. Intrauterine pressure (IUP) was recorded using an intrauterine double-chip microcatheter (Urobar 8 DS-F, Raumedic, Rehau AG & Co., Rehau, Germany). Differences in pressure (ΔP) and area under the curve (ΔAUC) after drug administration in the uterine body and uterine horn in the various dilution series were noted. A paired Student's t-test was used to evaluate differences between groups, with significance set at P < 0.05.

Results

A significant initial increase in uterine activity was visible at each dosage. Inhibition of uterine activity was seen over longer periods of 5 and 10 min, particularly for a medium-dose range of 1–2 mg/ml. At a dosage of 2 mg/ml in particular, celandine almost always led to significant values.

Conclusion

Following intra-arterial administration in a swine uterus perfusion model, celandine initially causes a significant increase in contractility, which is followed over time by a relaxation phase. This suggests interesting hypotheses on whether Chelidonium majus might be used to promote targeted sperm transport.  相似文献   
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