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991.
An examination of cardiovascular collapse induced by eastern brown snake (Pseudonaja textilis) venom
Janeyuth Chaisakul Geoffrey K. Isbister Sanjaya Kuruppu Nicki Konstantakopoulos Wayne C. Hodgson 《Toxicology letters》2013
The Pseudonaja genus (Brown snakes) is widely distributed across Australia and bites account for significant mortality. Venom-induced consumption coagulopathy (VICC) and, less often, early cardiovascular collapse occur following envenoming by these snakes. We have previously examined possible mechanism(s) behind the early cardiovascular collapse following Papuan taipan (Oxyuranus scutellatus) envenoming. In the present study, we investigate early cardiovascular collapse in anaesthetized rats following administration of eastern brown snake (Pseudonaja textilis) venom, and prevention of this effect with prior administration of ‘priming’ doses (i.e. doses of venom which caused a transient hypotensive response) of venom. P. textilis venom (5–10 μg/kg, i.v.) induced cardiovascular collapse in anaesthetized rats, characterized by a rapid decrease in systolic blood pressure until non recordable. Prior administration of ‘priming’ doses of P. textilis venom (2 and 3 μg/kg) or, at least, 4–5 doses of O. scutellatus (2 μg/kg, i.v.) or Daboia russelii limitis (20 μg/kg, i.v.) venoms prevented cardiovascular collapse induced by P. textilis venom. Moreover, early collapse was also inhibited by prior administration of 2 discrete doses of Acanthophis rugosus venom. Prior administration of commercial polyvalent snake antivenom (500–3000 units/kg, i.v.) or heparin (300 units/kg, i.v.) also inhibited P. textilis venom-induced cardiovascular collapse. Our results indicate that P. textilis venom-induced cardiovascular collapse can be prevented by prior administration of sub-lethal doses of venom from P. textilis, O. scutellatus, A. rugosus and D. russelii limitis. This suggests that sudden cardiovascular collapse following envenoming is likely to involve a common mechanism/pathway activated by different snake venoms. 相似文献
992.
《Inhalation toxicology》2013,25(14):1174-1183
The Borgwaldt RM20S® smoking machine enables the generation, dilution, and transfer of fresh cigarette smoke to cell exposure chambers, for in vitro analyses. We present a study confirming the precision (repeatability r, reproducibility R) and accuracy of smoke dose generated by the Borgwaldt RM20S® system and delivery to exposure chambers. Due to the aerosol nature of cigarette smoke, the repeatability of the dilution of the vapor phase in air was assessed by quantifying two reference standard gases: methane (CH4, r between 29.0 and 37.0 and RSD between 2.2% and 4.5%) and carbon monoxide (CO, r between 166.8 and 235.8 and RSD between 0.7% and 3.7%). The accuracy of dilution (percent error) for CH4 and CO was between 6.4% and 19.5% and between 5.8% and 6.4%, respectively, over a 10–1000-fold dilution range. To corroborate our findings, a small inter-laboratory study was carried out for CH4 measurements. The combined dilution repeatability had an r between 21.3 and 46.4, R between 52.9 and 88.4, RSD between 6.3% and 17.3%, and error between 4.3% and 13.1%. Based on the particulate component of cigarette smoke (3R4F), the repeatability (RSD?=?12%) of the undiluted smoke generated by the Borgwaldt RM20S® was assessed by quantifying solanesol using high-performance liquid chromatography with ultraviolet detection (HPLC/UV). Finally, the repeatability (r between 0.98 and 4.53 and RSD between 8.8% and 12%) of the dilution of generated smoke particulate phase was assessed by quantifying solanesol following various dilutions of cigarette smoke. The findings in this study suggest the Borgwaldt RM20S® smoking machine is a reliable tool to generate and deliver repeatable and reproducible doses of whole smoke to in vitro cultures. 相似文献
993.
Dan Zhang Min Zhang Bao Ding Zong-Yin Qiu 《Journal of Asian natural products research》2013,15(4):297-303
A novel, water-soluble 20-hydroxylecdysono-20,22-phosphoric acid 2 and its sodium salt 3 were designed and synthesized from 20-hydroxylecdysone 1 in six steps and with 67% overall yield. The synthesized phosphoric acid 2 exhibited hypoglycemic activity >40-fold more potent than that of 20-hydroxylecdysone 1 at concentrations between 2 × 10? 7 and 2 × 10? 8 mol/l in a glucose consumption test in HepG2 cells. At a concentration of 2 × 10? 9 mol/l, phosphoric acid 2 was still active, causing a maximum increase in glucose consumption of more than 500%, while 20-hydroxylecdysone 1 was inactive. 相似文献
994.
N. Yayli N. Yildirim N. Doğan A. Usta L. Altun 《Journal of Asian natural products research》2013,15(5):771-775
One new triterpene compound, 3β-acetoxylup-20(30)-en-29-al (1) and two known 3-acetylptiloepoxide (2) and 3β-acetoxylup-20(29)-ene (3) were isolated for the first time from the leaves of Campanula lactiflora and their structures were deduced by high field 1D and 2D 400 MHz NMR, EI-MS and (+) LC-MS/MS spectra. 相似文献
995.
Hui-Yuan Gao Di Wu Chuan Lu Xiao-Min Xu Jian Huang Bo-Hang Sun 《Journal of Asian natural products research》2013,15(2):144-149
In the screening of biologically active constituents from medicinal plants, the 75% EtOH extract of the testas of Castanea mollissima Blume showed potent α-glucosidase inhibitory activity. By means of various chromatographic methods, the extract gave a new dammarane-type triterpene 1 along with 17 known compounds. The structure of 1 was determined to be 3β-acetoxy-20-oxo-21-nordammaran-23-oic acid by HRMS and NMR studies including 2D NMR experiments. The new compound and some known compounds showed potent α-glucosidase inhibitory activity with acarbose as a positive control. 相似文献
996.
Feng Wang Zhan-Lin Li Hong-Hua Cui Hui-Ming Hua Yong-Kui Jing Sheng-Wang Liang 《Journal of Asian natural products research》2013,15(3):193-197
Two new triterpenoids, 3-oxotirucalla-7,9(11),24-trien-21-oic acid (1) and 18Hα,3β,20β-ursanediol (2), along with 15 known triterpenes, α-amyrin, α-boswellic acid, β-boswellic acid, acetyl α-boswellic acid, acetyl β-boswellic acid, 9,11-dehydro-β-boswellic acid, 9,11-dehydro-α-boswellic acid, acetyl 11α-methoxy-β-boswellic acid, 11-keto-β-boswellic acid, acetyl 11-keto-β-boswellic acid, acetyl α-elemolic acid, 3β-hydroxytirucalla-8,24-dien-21-oic acid, elemonic acid, 3α-hydroxytirucalla-7,24-dien-21-oic acid, and 3α-hydroxytirucall-24-en-21-oic acid, were isolated from the resin of Boswellia carterii Birdw. 相似文献
997.
Patrycja Kleczkowska Engin Bojnik Anna Leśniak Piotr Kosson Isabelle Van den Eynde Steven Ballet Sandor Benyhe Dirk Tourwé Andrzej W. Lipkowski 《Pharmacological reports : PR》2013,65(4):836-846
BackgroundRecently, we presented a novel compound (PK20, Dmt-D-Lys-Phe-Phe-Lys-Lys-Pro-Phe-Tle-Leu-OH) that targets single entity opioid and neurotensin pharmacophores. This endomorphin-2-like opioid peptide was introduced as a highly active analgesic because it elicited a strong dose- and time-dependent antinociceptive response when administered centrally and peripherally. Its pain-relieving activity was observed as rapidly as 5 min after drug injection. Such promising results led us to perform further studies, such as determining the resistance to enzymatic degradation, which resulted in obtaining a very stable opioid pharmacore PK20 metabolite.MethodsThe synthesis of PK20 and its N-terminal tetrapeptide fragment has been accomplished using solid phase peptide chemistry. The biological stability of peptides has been measured in human serum and analyzed by HPLC/MS. Peptides were pharmacologically characterized in in vitro MOP and DOP receptor binding as well as [35S]GTPγS receptor binding assays. Antinociceptive properties of compounds were measured by in vivo assays in C57Bl6 mice after intravenous or intrathecal applications.ResultsDmt-D-Lys-Phe-Phe-OH (PK20M), an N-terminal tetrapeptide metabolite of the opioid-neurotensin hybrid peptide PK20, is characterized by a long duration of action, as demonstrated by a preserved, long-lasting analgesic effect even 2 h post-injection (average % MPE = 69.33). In rat brain membranes, PK20M efficiently displaced both the MOP and DOP receptor selective radioprobes [3H]DAMGO and [3H]DIDI (pKi of 9.52 and 7.86, respectively) and potently stimulated [35S]GTPγS binding, proving full agonism at both receptor types. In the [35S]GTPγS assay, which measured the agonist-mediated G protein activation, PK20M together with PK20 and Met-enkephalin were potent stimulators of the regulatory G proteins. The relative affinities of PK20M for the μ and δ receptor subtypes revealed μ-receptor selectivity.ConclusionThe novel MOP receptor selective metabolite has been shown to possess opioid subtype receptor selectivity, high potency, and effective analgesic activities as measured in various bioassays. 相似文献
998.
Jianda Zhou Rui Liu Chengqun Luo Xiao Zhou Kun Xia Xiang Chen Ming Zhou Qiong Zou Peiguo Cao Ke Cao 《Cancer biology & therapy》2014,15(10):1340-1349
Background
MicroRNA-20a (miR-20a) plays a key role in tumorigenesis and progression. But its function is reverse in different kinds of malignant tumor, and its role and mechanism in cutaneous squamous cell carcinoma (CSCC) remains unclear.
Object
To determine the miR-20a’s roles in CSCC and confirm whether LIMK1 is a direct target gene of miR-20a.
Methods
First miR-20a and LIMK1 expression levels were detected in six pairs of CSCC tissues and corresponding normal skin by qRT-PCR. Then MTT assays and colony formation assays were performed to evaluate the impact of miR-20a on cell proliferation. In addition, scratch migration assays and transwell invasion assays were performed to check miR-20a’s effect on cell metastasis. Since LIMK1 (LIM kinase-1) was predicted as a target gene of miR-20a, the changes of LIMK1 protein and mRNA were measured by western blot and qRT-RCR methods after miR-20a overexpression. Moreover the dual reporter gene assay was performed to confirm whether LIMK1 is a direct target gene of miR-20a. Finally LIMK1 mRNA and miR-20a in other 30 cases of CSCC pathological specimens were determined and a correlation analysis was evaluated.
Results
The miR-20a significantly low-expressed in CSCC tissues compared with that in matched normal tissues while LIMK1 has a relative higher expression. MiR-20a inhibited A431 and SCL-1 proliferation and metastasis. Both of LIMK1 protein and mRNA levels were downregulated after miR-20a overexpression. The dual reporter gene assays revealed that LIMK1 is a direct target gene of miR-20a. Furthermore, qRT-PCR results of LIMK1 mRNA and miR-20a in 30 cases of CSCC pathological specimens showed miR-20a is inversely correlated with LIMK1 expression.
Conclusion
Our study demonstrated that miR-20a is involved in the tumor inhibition of CSCC by directly targeting LIMK1 gene. This finding provides potential novel strategies for therapeutic interventions of CSCC. 相似文献
999.
1000.
目的观察针灸治疗Ⅰ度子宫脱垂的临床疗效。方法将60例Ⅰ度子宫脱垂患者随机分为治疗组和对照组,每组30例,对照组采用支持疗法和盆底肌肉锻炼,治疗组在对照组的基础上施以维道透刺关元、提托透刺子宫断续波电针配合温和灸百会治疗。治疗3个月后比较两组临床疗效及治疗前后PFDI-20短表评分。结果治疗组总有效率为90.0%,对照组为40.0%,两组比较差异具有统计学意义(P0.01)。治疗组治疗后PFDI-20短表各项评分与同组治疗前比较,差异均具有统计学意义(P0.05)。对照组治疗后PFDI-20、POPDI-6和CARDI-8与同组治疗前比较,差异均具有统计学意义(P0.05)。治疗组治疗后PFDI-20短表各项评分与对照组比较,差异均具有统计学意义(P0.01,P0.05)。结论透刺电针配合灸百会是一种治疗子宫脱垂的有效方法。 相似文献