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991.
Jin-Wook Yoo Samir Mitragotri 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(25):11205-11210
Particle engineering for biomedical applications has unfolded the roles of attributes such as size, surface chemistry, and shape for modulating particle interactions with cells. Recently, dynamic manipulation of such key properties has gained attention in view of the need to precisely control particle interaction with cells. With increasing recognition of the pivotal role of particle shape in determining their biomedical applications, we report on polymeric particles that are able to switch their shape in real time in a stimulus-responsive manner. The shape-switching behavior was driven by a subtle balance between polymer viscosity and interfacial tension. The balance between the two forces was modulated by application of an external stimulus chosen from temperature, pH, or chemical additives. The dynamics of shape switch was precisely controlled over minutes to days under physiological conditions. Shape-switching particles exhibited unique interactions with cells. Elliptical disk-shaped particles that are not phagocytosed by macrophages were made to internalize through shape switch, demonstrating the ability of shape-switchable particles in modulating interaction with cells. 相似文献
992.
Byeong-Churl Jang Jong-Gu Park Dae-Kyu Song Won-Ki Baek Sun Kyun Yoo Kyung-Hwan Jung Gy-Young Park Tae-Yun Lee Seong-Il Suh 《Toxicology in vitro》2009,23(2):281-287
Sanguinarine is a plant-derived benzophenanthridine alkaloid and has been shown to possess anti-tumor activities against various cancer cells. In this study, we investigated whether sanguinarine induces apoptosis in A549 human lung cancer cells. Treatment of A549 cells with sanguinarine induced apoptosis in a dose- and time-dependent manner. Treatment with sanguinarine led to activation of caspases and MAPKs as well as increased MKP-1 expression. Importantly, pretreatment with z-VAD-fmk, a pan caspase inhibitor suppressed the sanguinarine-induced apoptosis in A549 cells. Moreover, pretreatment with NAC, a sulfhydryl group-containing reducing agent strongly suppressed the apoptotic response and caspase activation to sanguinarine. However, the sanguinarine-mediated cytotoxicity in A549 cells was not protected by pharmacological inhibition of MAPKs or MKP-1 siRNA-mediated knockdown of MKP-1. These results collectively suggest that sanguinarine induces apoptosis in A549 cells through cellular glutathione depletion and the subsequent caspase activation. 相似文献
993.
S Pierno GM Camerino V Cippone J-F Rolland J-F Desaphy A De Luca A Liantonio G Bianco JD Kunic AL George Jr D Conte Camerino 《British journal of pharmacology》2009,156(8):1206-1215
Background and purpose:
Statins and fibrates can produce mild to life-threatening skeletal muscle damage. Resting chloride channel conductance (gCl), carried by the ClC-1 channel, is reduced in muscles of rats chronically treated with fluvastatin, atorvastatin or fenofibrate, along with increased resting cytosolic calcium in statin-treated rats. A high gCl, controlled by the Ca2+-dependent protein kinase C (PKC), maintains sarcolemma electrical stability and its reduction alters muscle function. Here, we investigated how statins and fenofibrate impaired gCl.Experimental approach:
In rats treated with fluvastatin, atorvastatin or fenofibrate, we examined the involvement of PKC in gCl reduction by the two intracellular microelectrodes technique and ClC-1 mRNA level by quantitative real time-polymerase chain reaction. Direct drug effects were tested by patch clamp analysis on human ClC-1 channels expressed in human embryonic kidney (HEK) 293 cells.Key results:
Chelerythrine, a PKC inhibitor, applied in vitro on muscle dissected from atorvastatin-treated rats fully restored gCl, suggesting the involvement of this enzyme in statin action. Chelerythrine partially restored gCl in muscles from fluvastatin-treated rats but not in those from fenofibrate-treated rats, implying additional mechanisms for gCl impairment. Accordingly, a decrease of ClC-1 channel mRNA was found in both fluvastatin-and fenofibrate-treated rat muscles. Fenofibric acid, the in vivo metabolite of fenofibrate, but not fluvastatin, rapidly reduced chloride currents in HEK 293 cells.Conclusions and implications:
Our data suggest multiple mechanisms underlie the effect of statins and fenofibrate on ClC-1 channel conductance. While statins promote Ca2+-mediated PKC activation, fenofibrate directly inhibits ClC-1 channels and both fluvastatin and fenofibrate impair expression of mRNA for ClC-1. 相似文献994.
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998.
Lee JY Choi JY Lee KM Park SK Han SH Noh DY Ahn SH Kim DH Hong YC Ha E Yoo KY Ambrosone CB Kang D 《Clinica chimica acta; international journal of clinical chemistry》2008,389(1-2):167-170
BACKGROUND: Hypoxia inducible factor 1 alpha (HIF-1A) is activated by low oxygen condition tension, a key regulator of the gene involved in the cellular response to hypoxia. Tumors exhibiting extensive hypoxia are more aggressive than tumors oxygenized better. METHODS: To evaluate the potential role of the polymorphisms of HIF-1A in the etiology of breast cancer, histologically confirmed incident breast cancer cases (n=1599) and control subjects (n=1536) were recruited. RESULTS: Two selected SNPs (Ex15+197C>T and P582S) were not associated with overall breast cancer risk (TT vs. CC: OR=0.9, 95% CI=0.6-1.5, Ser/Ser vs. Pro/Pro: OR=5.5, 95% CI=0.7-45.4, respectively). However, when stratified analyses were performed, significant associations were observed between Ser/Ser genotype at codon 582 and breast cancer risk among women with larger tumor size (>2 cm) (OR=10.1, 95% CI=1.1-91.1) or without lymph node involvement (OR=9.3, 95% CI=1.1-79.4), although confidence intervals were wide. CONCLUSIONS: Our findings support the hypothesis that the HIF-1Alpha P582S variant may confer susceptibility to subgroups of breast cancer in Korean women. However, further study is warranted due to low statistical power caused by very low minor allele frequencies. 相似文献
999.
Human sperm devoid of PLC, zeta 1 fail to induce Ca(2+) release and are unable to initiate the first step of embryo development
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Yoon SY Jellerette T Salicioni AM Lee HC Yoo MS Coward K Parrington J Grow D Cibelli JB Visconti PE Mager J Fissore RA 《The Journal of clinical investigation》2008,118(11):3671-3681
Egg activation, which is the first step in the initiation of embryo development, involves both completion of meiosis and progression into mitotic cycles. In mammals, the fertilizing sperm delivers the activating signal, which consists of oscillations in free cytosolic Ca(2+) concentration ([Ca(2+)](i)). Intracytoplasmic sperm injection (ICSI) is a technique that in vitro fertilization clinics use to treat a myriad of male factor infertility cases. Importantly, some patients who repeatedly fail ICSI also fail to induce egg activation and are, therefore, sterile. Here, we have found that sperm from patients who repeatedly failed ICSI were unable to induce [Ca(2+)](i) oscillations in mouse eggs. We have also shown that PLC, zeta 1 (PLCZ1), the sperm protein thought to induce [Ca(2+)](i) oscillations, was localized to the equatorial region of wild-type sperm heads but was undetectable in sperm from patients who had failed ICSI. The absence of PLCZ1 in these patients was further confirmed by Western blot, although genomic sequencing failed to reveal conclusive PLCZ1 mutations. Using mouse eggs, we reproduced the failure of sperm from these patients to induce egg activation and rescued it by injection of mouse Plcz1 mRNA. Together, our results indicate that the inability of human sperm to initiate [Ca(2+)](i) oscillations leads to failure of egg activation and sterility and that abnormal PLCZ1 expression underlies this functional defect. 相似文献
1000.
Plasmid-mediated quinolone resistance determinants qnrA, qnrB, and qnrS among clinical isolates of Enterobacteriaceae in a Korean hospital 总被引:1,自引:0,他引:1
Tamang MD Seol SY Oh JY Kang HY Lee JC Lee YC Cho DT Kim J 《Antimicrobial agents and chemotherapy》2008,52(11):4159-4162
Screening of 368 consecutive nonreplicate clinical isolates of Enterobacteriaceae resistant to nalidixic acid and at least one extended-spectrum β-lactam revealed the presence of qnrA, qnrB, and qnrS determinants, and identified novel qnrB variants, in Citrobacter freundii isolates. This study also revealed, for the first time, the linkage of qnrB, armA, and extended-spectrum and/or AmpC-type β-lactamase genes on large conjugative plasmids. 相似文献