全文获取类型
收费全文 | 14541篇 |
免费 | 862篇 |
国内免费 | 554篇 |
专业分类
耳鼻咽喉 | 26篇 |
儿科学 | 279篇 |
妇产科学 | 104篇 |
基础医学 | 1675篇 |
口腔科学 | 132篇 |
临床医学 | 1334篇 |
内科学 | 3163篇 |
皮肤病学 | 140篇 |
神经病学 | 729篇 |
特种医学 | 233篇 |
外科学 | 879篇 |
综合类 | 2169篇 |
现状与发展 | 1篇 |
预防医学 | 661篇 |
眼科学 | 89篇 |
药学 | 3354篇 |
5篇 | |
中国医学 | 684篇 |
肿瘤学 | 300篇 |
出版年
2023年 | 102篇 |
2022年 | 247篇 |
2021年 | 376篇 |
2020年 | 373篇 |
2019年 | 261篇 |
2018年 | 326篇 |
2017年 | 310篇 |
2016年 | 384篇 |
2015年 | 356篇 |
2014年 | 686篇 |
2013年 | 1178篇 |
2012年 | 708篇 |
2011年 | 797篇 |
2010年 | 662篇 |
2009年 | 590篇 |
2008年 | 694篇 |
2007年 | 683篇 |
2006年 | 629篇 |
2005年 | 598篇 |
2004年 | 559篇 |
2003年 | 547篇 |
2002年 | 459篇 |
2001年 | 416篇 |
2000年 | 389篇 |
1999年 | 341篇 |
1998年 | 291篇 |
1997年 | 314篇 |
1996年 | 275篇 |
1995年 | 231篇 |
1994年 | 214篇 |
1993年 | 187篇 |
1992年 | 187篇 |
1991年 | 157篇 |
1990年 | 148篇 |
1989年 | 132篇 |
1988年 | 125篇 |
1987年 | 110篇 |
1986年 | 111篇 |
1985年 | 135篇 |
1984年 | 148篇 |
1983年 | 83篇 |
1982年 | 91篇 |
1981年 | 85篇 |
1980年 | 71篇 |
1979年 | 34篇 |
1978年 | 34篇 |
1977年 | 27篇 |
1976年 | 22篇 |
1975年 | 16篇 |
1974年 | 22篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
101.
采用免疫组织化学、免疫电子显微镜及高效液相结合放射免疫学方法,研究人和 Wistar 大鼠心包,结果表明:心包组织中存在 ANF 和 AngⅡ样物质。在采用兔抗 ANF 为抗体时,心包组织的间皮细胞存在明显的金粒子标记颗粒,间皮细胞是主要的内分泌细胞。心包组织存在 Ang Ⅱ和3种分子形式ANF.本研究提示.心包除已知功能外,尚存在重要的内分泌功能. 相似文献
102.
A. Fjellestad-Paulsen L. d’Agay-Abensour P. Höglund J.-C. Rambaud 《European journal of clinical pharmacology》1996,50(6):491-495
Objective: The bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin (dDAVP), with and without an enzyme inhibitor,
was studied in six healthy, male volunteers aged 19–34 years, followed for 8 h after each drug administration.
Methods:
For i.v. administration the subjects received 4 μg dDAVP. For intestinal administration 500 μg dDAVP was administered directly,
in two separate sessions, in the first part of the duodenum via a triple-lumen channel tube. In one session a solution of
isotonic polyethylene glycol (PEG) was given as a continuous enteral perfusion. In the other session a solution of PEG and
aprotinin was administered enterally at the constant rate of 5 ml⋅min−1 for 4 h. Plasma dDAVP was measured using a specific, sensitive radioimmunoassay and intestinal juice was collected for measurement
of lipase, chymotrypsin and pH every 30 min for 5 h.
Results:
The intestinal chymotrypsin activity was decreased after perfusion of aprotinin while the lipase activity was not modified.
After i.v. administration, the half-life of elimination of dDAVP was 1.56 h and plasma clearance 1.24 ml⋅min⋅kg−1. The mean bioavailability after duodenal administration of dDAVP + aprotinin was 0.46% compared with 0.09% after duodenal
administration of dDAVP alone. The bioavailability of dDAVP after direct duodenal administration of an aqueous solution was
similar to that after swallowing a tablet in a previous study and increased 5 times when given together with a perfusion of
an enzyme inhibitor.
Received: 27 October 1995/Accepted in revised form: 26 February 1996 相似文献
103.
目的 探讨血管紧张素转化酶2(ACE2)对缺氧复氧诱导的肾小管上皮细胞HK-2氧化应激、炎症、凋亡及核因子E2相关因子2(Nrf2)/血红素加氧酶1(HO-1)信号通路的影响。 方法 将ACE2慢病毒转染HK-2细胞,按照实验需要分为常氧组(Control组)、缺氧复氧模型组(H/R组)、缺氧复氧转染阴性对照慢病毒组(H/R-NC组)和缺氧复氧转染ACE2慢病毒组(H/R-ACE2组)。细胞经H/R处理后,通过CCK-8法检测细胞活力;RT-PCR及ELISA法检测炎症因子白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和白介素-1β(IL-1β)水平;比色法检测超氧化物歧化酶(SOD)、丙二醛(MDA)表达水平;Western blotting法检测胱天蛋白酶3(Caspase-3)、B淋巴细胞瘤-2基因(Bcl-2)、Bcl-2关联X蛋白(Bax)、Nrf2、HO-1的蛋白水平。采用Nrf2抑制剂ML385以及HO-1抑制剂SnPPIX抑制Nrf2/HO-1通路,Western blotting法检测Caspase-3、Bcl-2、Bax、Nrf2、HO-1的蛋白表达水平变化,比色法检测SOD和MDA表达变化。 结果 与Control组相比,H/R组细胞活力降低(t=7.58,P<0.001),MDA含量和炎症因子IL-6、TNF-α和IL-1β表达水平以及细胞凋亡相关蛋白Caspase-3、Bax蛋白水平均增加(tMDA=11.08,PMDA<0.001;tPCR-IL-6=5.82,PPCR-IL6<0.001;tPCR-TNF-α=7.69,PPCR-TNF-α<0.001;tPCR-IL-1β=4.80,PPCR-IL-1β=0.001;tELISA-IL-6=34.11,PELISA-IL-6<0.001;tELISA-TNF-α=14.12,PELISA-TNF-α<0.001;tELISA-IL-1β=9.63,PELISA-IL-1β<0.001;tCaspase-3=2.73,PCaspase-3=0.026;tBax=27.75,PBax<0.001),SOD活性、Bcl-2和ACE2蛋白水平下降(tSOD=7.74,PSOD<0.001;tBcl-2=75.49,PBcl-2<0.001;tACE2=11.41,PACE2<0.001)。与H/R组相比,H/R-ACE2组细胞活力增加(t=3.61,P=0.002),MDA含量和炎症因子IL-6、TNF-α和IL-1β表达水平以及细胞凋亡相关蛋白Caspase-3、Bax蛋白水平均下降(tMDA=6.15,PMDA<0.001;tPCR-IL-6=3.34,PPCR-IL-6=0.006;tPCR-TNF-α=3.65,PPCR-TNF-α=0.007;tPCR-IL-1β=4.06,PPCR-IL-1β=0.004;tELISA-IL-6=14.62,PELISA-IL-6<0.001;tELISA-TNF-α=10.42,PELISA-TNF-α<0.001;tELISA-IL-1β=8.65,PELISA-IL-1β<0.001;tCaspase-3=3.74,PCaspase-3=0.006;tBax=30.52,PBax<0.001),SOD活性、Bcl-2和ACE2蛋白水平增加(tSOD=3.58,PSOD=0.007;tBcl-2=63.86,PBcl-2<0.001;tACE2=58.72,PACE2<0.001),Nrf2/HO-1信号通路被激活蛋白水平增加(tNrf2=44.55,PNrf2<0.001;tHO-1=14.19,PHO-1<0.001)。然而ML385和SnPPIX处理会抑制ACE2基因过表达在H/R中HK-2细胞的保护作用(FBax=11.02,PBax=0.003;FBcl-2=21.48,PBcl-2<0.001;FCaspase-3=20.80,PCaspase-3<0.001;FSOD=133.49,PSOD<0.001;FMDA=14.06,PMDA=0.001)。 结论 ACE2在HK-2细胞缺氧复氧损伤中具有抑制氧化应激、调节炎症、改善凋亡的作用,Nrf2/HO-1信号通路发挥重要作用。 相似文献
104.
Franz Buchegger Mai Phan Denis Rivier Stephan Carrel Roberto S. Accolla Jean-Pierre Mach 《Journal of immunological methods》1982,49(2):129-139
A solid-phase enzyme immunoassay using both mouse monoclonal and goat polyclonal antibodies against carcinoembryonic antigen (CEA) was developed. The assay detects 0.6 to 1.2 ng of CEA per ml of serum and has 3 incubation steps which can be performed in 1 day. Polystyrene balls coated with polyclonal goat anti-CEA antibodies are first incubated with heat-extracted serum samples. Bound CEA is then detected by addition of mouse monoclonal antibodies, followed by goat IgG anti-mouse IgG1 coupled to alkaline phosphatase. Results with this enzyme immunoassay using monoclonal antibodiies (M-EIA) have been compared with those obtained by the conventional inhibition radioimmunoassay (RIA) using goat antiserum. Three hundred and eighty serum samples from 167 patients with malignant or non-malignant diseases and from 134 normal individuals with or without heavy smoking habits were analyzed by the 2 assays. Excellent correlation between the results of the 2 assays was obtained, but the M-EIA, using monoclonal antibodies from a single hybridoma, did not discriminate better than the conventional RIA between CEA produced by different types of carcinoma and between CEA associated with malignant or non-malignant diseases. Follow-up studies of several patients by sequential CEA determinations with the 2 assays showed that the M-EIA was as accurate as the RIA for the detection of tumor recurrences. 相似文献
105.
We have identified an autoantigen that is recognized by antibodies from an 18-year-old female with a history of recurrent infections who later in her clinical course developed Raynaud's phenomenon and telangiectasias. By indirect immunofluorescence (IIF), the index serum produced a unique cytoplasmic discrete speckled (CDS) staining pattern that partially colocalized with early endosome antigen 1 (EEA1) but not Golgi complex or other cytoplasmic organelles in HEp-2 cells. When HEp-2 cells were treated with 0.1 N HCl, the cytoplasmic speckled staining of the index serum was markedly decreased, suggesting that the reactive antigen was soluble. Western blot analysis showed a reactive approximately 97 kDa protein in a saline soluble protein preparation from HeLa cells. Mass spectrometric analysis of the excised 97 kDa band that was immunoprecipitated from HeLa cell extracts identified GRASP-1 as a possible target. The index serum and anti-GRASP-1 antibodies colocalized to structures in the cytoplasm of HEp-2 cells. Synthetic peptides representing the full-length GRASP-1 protein were used to identify reactive epitopes. Like many other cytoplasmic autoantigens, GRASP-1 has numerous coiled-coil domains throughout the protein with the exception of short segments at the amino and carboxyl terminus. 相似文献
106.
We sought to confirm the identity of the tachykinin receptor subtype that mediates plasma extravasation in the rat trachea, and assess the respective contributions of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) in regulating this tachykinin-induced response. To achieve these aims, we determined the relative potencies of several natural tachykinins and receptor-selective synthetic agonists, both before and after inhibiting NEP with phosphoramidon and ACE with captopril. We also determined the effects of these peptidase inhibitors, and the NK-1 receptor antagonist L-703,606, on the plasma extravasation produced by capsaicin, which releases tachykinins endogenously from sensory nerve endings. We found that the rank order of potency for producing plasma extravasation in the rat trachea was NK-1 receptor agonist ([Sar9, Met(O2)11] SP)>substance P>neurokinin A> neurokinin B. The NK-2 ([Nle10]NKA (4–10)) and NK-3 ([MePhe7]NKB) receptor agonists were without effect. We observed no change in the relative potencies of these peptides after giving rats phosphoramidon or captopril, which suggests that the different peptide potencies are not simply the consequence of different rates of enzymatic degradation. Nevertheless, the responses to substance P and neurokinin A were clearly potentiated in rats given phosphoramidon, indicating that NEP effectively degrades tachykininsin vivo. No significant potentiation was evident for any peptide in rats given captopril. Similarly, the plasma extravasation produced by capsaicin was potentiated in rats given phosphoramidon, but not in those given captopril. Pretreating rats with L-703,606 abolished the response to capsaicin. We conclude from these observations that NK-1 receptors mediate tachykinin-induced plasma extravasation in the rat trachea, and that NEP regulates this response with little or no contribution from ACE. 相似文献
107.
Sadataka Inuzuka Takato Ueno Hideo Tateishi Takuji Torimura Michio Sata Kyuichi Tanikawa Masamichi Kojiro 《Pathology international》1994,44(5):391-397
Elevation of the serum angiotensin-converting enzyme (sACE) level and hepatic granulomas were found during a clinical relapse in a 22 year old patient with acute viral hepatitis type A (AVH-A). The serum transaminase level and sACE level remained high for more than 6 months. In the biopsied specimen of the liver, fibrous rings of granulomas composed of collagen types I, III, and V were observed. Furthermore, the localization of ACE was visible in the rough endoplasmic reticulum of epithelioid cells of granulomas in the liver under electron microscopy using the indirect immunoperoxidase method. These results suggest that granuloma cells in the liver caused by hepatitis A may be involved in ACE production. In addition, other diseases associated with the presence of granulomas in the liver, such as lymphoma, cytomegalovirus infection, visceral leishmaniasis, and lupoid hepatitis, were ruled out. However, the hepatic granulomas disappeared with the healing of AVH-A. In this regard, the present case is considered to be one of the very few cases of hepatic sarcoidosis. 相似文献
108.
Comparative study of pituitary and bacteria-derived human growth hormone by monoclonal antibodies 总被引:1,自引:0,他引:1
We have established hybridoma lines which secrete mouse monoclonal antibodies (Mabs) to human pituitary growth hormone, hGH. Using indirect competitive ELISA and indirect passive hemagglutination inhibition twelve different Mabs were characterized with regard to cross-reactivity with the hGH-related hormones, human chorionic somatomammotropin, hCS, and human prolactin, hPRL. The reactivity of these Mabs with pituitary hGH was compared to that with either bacterially-produced methionyl-hGH or to that of reduced and S-carboxymethylated hGH, which has an altered conformation. None of the Mabs reacted with hPRL. Four did not react with hCS whereas the others showed varying degree of cross-reactivity with hCS. All Mabs reacted more weakly with reduced and S-carboxymethylated hGH than with the native form of the hormone, which was not seen with conventional rabbit antisera to hGH. Thus in the case of hGH the Mabs are superior to conventional antisera in revealing small conformational differences. However the pituitary and bacterially-derived methionyl-hGH were indistinguishable as determined by the 12 Mabs. 相似文献
109.
110.
Role of ubiquitin-mediated proteolysis in the pathogenesis of neurodegenerative disorders 总被引:5,自引:0,他引:5
Intraneuronal inclusions containing ubiquitylated filamentous protein aggregates are a common feature of many of the major human neurodegenerative disorders, including Alzheimer's and Parkinson's disease. Loss of function mutations in enzymes of the ubiquitin conjugation/deconjugation pathway are sufficient to cause familial forms of neurodegenerative diseases, suggesting that failure of ubiquitin-mediated proteolysis could also be central to inclusion formation in the more common sporadic cases. Examination of ubiquitin-positive inclusions at the protein level provides evidence of attempted proteasomal proteolysis, however close inspection of the temporal aspects of inclusion formation indicates that ubiquitylation is probably a late event. In this regard, the presence of ubiquitin within inclusions of idiopathic neurodegenerative disorders may indicate not a primary dysfunction of ubiquitin-mediated proteolysis, but rather a secondary, presumably protective cellular response. Within this model, other factors are likely to be initiating in inclusion biogenesis. Consistent with these proposals, non-ubiquitylated forms of the principal ubiquitylated components of Alzheimer's disease neurofibrillary tangles and Parkinson's disease Lewy bodies, tau and alpha-synuclein proteins, respectively, can be degraded by proteasomes in a pathway which does not have an absolute requirement for ubiquitylation. Inhibition of proteasome function in the pathological state, as has been reported in both Alzheimer's and Parkinson's disease, could therefore contribute both to accumulation of non-ubiquitylated forms of aggregation-prone neuronal proteins, as well as impaired clearance of ubiquitylated aggregates. 相似文献