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91.
Abstract: varicella is a common childhood disease with a typical exanthem. We present four children with severe, localized disease, all associated with some form of trauma to the skin during the incubation period: a 3½-year-old boy sustained wasp stings on the hand, a 5-year-old boy received extensive sun exposure, a neonate had latrogenic trauma to her arm, and a 13-year-old boy underwent knee arthroscopy and was wearing a cast. It is postulated that such injuries to the skin either allowed more virus-infected cells to enter the skin at the sites, or that factors such as insect venom and ultraviolet light altered local immunity to varicella zoster virus. 相似文献
92.
Celia Montero R.Tomasz Smolenski John A. Duley H.Anne Simmonds 《Biochemical pharmacology》1990,40(12):2617-2623
The mechanism by which S-adenosylmethionine (SAM) and adenosine (Ado) increase ATP levels in intact human erythrocytes in vitro has been compared. The use of erythrocytes from healthy controls and from subjects totally deficient in adenine phosphoribosyltransferase (APRT), plus inhibitors of adenosine kinase (AK) and adenosine deaminase (ADA) separately and together, has enabled us to demonstrate that this increment in ATP levels occurred via totally different metabolic routes. The results show that: (i) whilst the Ado-induced increment in ATP was AK dependent, that produced by SAM was independent of AK; and (ii) the SAM-induced increment in ATP was totally dependent on APRT and that some of the increment produced by Ado might also be APRT dependent. The above data are consistent with the metabolism of SAM to ATP by a route recently identified by us whereby ATP is formed from deoxyadenosine: namely binding to the enzyme S-adenosylhomocysteine hydrolase with subsequent release of adenine and further conversion to ATP via APRT. 相似文献
93.
94.
Anne M Lewis Sheelu Varghese Hui Xu H Richard Alexander 《Journal of translational medicine》2006,4(1):48
The tumor microenvironment consists of tumor, immune, stromal, and inflammatory cells which produce cytokines, growth factors,
and adhesion molecules that promote tumor progression and metastasis. Of particular interest in this setting is interleukin-1
(IL-1), a pleiotropic cytokine with numerous roles in both physiological and pathological states. It is known to be up regulated
in many tumor types and has been implicated as a factor in tumor progression via the expression of metastatic and angiogenic
genes and growth factors. A number of studies have reported that high IL-1 concentrations within the tumor microenvironment
are associated with a more virulent tumor phenotype. Solid tumors in which IL-1 has been shown to be up regulated include
breast, colon, lung, head and neck cancers, and melanomas, and patients with IL-1 producing tumors have generally bad prognoses.
The exact mechanisms by which IL-1 promotes tumor growth remain unclear, though the protein is believed to act via induction
of pro-metastatic genes such as matrix metalloproteinases and through the stimulation of adjacent cells to produce angiogenic
proteins and growth factors such as VEGF, IL-8, IL-6, TNFα, and TGFβ. The IL-1 receptor antagonist (IL-1ra) is a naturally
occurring inhibitor to IL-1 and acts by binding to the IL-1 receptor without activating it. The protein has been shown to
decrease tumor growth, angiogenesis, and metastases in murine xenograft models. Our focus in this review is to summarize the
known data on the role of IL-1 in tumor progression and metastasis and the use of IL-1 inhibition as a novel therapeutic approach
in the treatment of solid organ malignancies. 相似文献
95.
96.
97.
98.
Jean-Fran?ois Ghersi-Egea Nathalie Strazielle Audrey Murat Anne Jouvet Annie Buénerd Marie-Fran?oise Belin 《Journal of cerebral blood flow and metabolism》2006,26(9):1165-1175
The choroid plexuses (CPs) form a protective interface between the blood and the ventricular cerebrospinal fluid (CSF). To probe into the pathways by which CPs provide brain protection, we sought to evaluate the efficiency of glutathione conjugation in this barrier as a mechanism to prevent the entry of blood-borne electrophilic, potentially toxic compounds into the CSF, and we investigated the fate of the resulting metabolites. Rat CPs, as well as human CPs from both fetal and adult brains, displayed high glutathione-S-transferase activities. Using an in vitro model of the blood-CSF barrier consisting of choroidal epithelial cells cultured in a two-chambered device, we showed that glutathione conjugation can efficiently prevent the entry of 1-chloro-2,4-dinitrobenzene (CDNB) into the CSF, a model for electrophilic compounds. The duration of this enzymatic protection was set by the concentration of CDNB to which the epithelium was exposed, and this barrier effect was impaired only on severe epithelial intracellular glutathione and cysteine depletion. The conjugate was excreted from the choroidal cells in a polarized manner, mostly at the blood-facing membrane, via a high-capacity transport process, which is not a rate-limiting step in this detoxification pathway, and which may involve transporters of the ATP-binding cassette c(Abcc) and/or solute carrier 21 (Slc21) families. Supplying the choroidal epithelium at the blood-facing membrane with a therapeutically relevant concentration of N-acetylcysteine sustained this neuroprotective effect. Thus, glutathione conjugation at the CP epithelium coupled with the basolateral efflux of the resulting metabolites form an efficient blood-CSF enzymatic barrier, which can be enhanced by pharmacologically increasing glutathione synthesis within the epithelial cells. 相似文献
99.
100.
M T Dao J P Villeneuve 《Clinical and investigative medicine. Médecine clinique et experimentale》1988,11(1):6-9
Triamterene is a potassium-sparing diuretic used in patients with cirrhosis for the treatment of ascites. It is extensively metabolized by the liver and is subject to an important first-pass effect after oral dosing. We examined the disposition and diuretic effect of triamterene after repeated oral administration (200 mg daily for 10 days) in 7 healthy controls and 6 patients with cirrhosis and ascites. In the controls the average plasma concentration of triamterene during a dosage interval was 45 +/- 8 ng/ml and that of hydroxy-triamterene sulfate, an active metabolite of triamterene, was 967 +/- 177 ng/ml. In the cirrhotics, the mean concentration of triamterene was 586 +/- 126 ng/ml (a 13-fold increase as compared with the controls) and that of hydroxy-triamterene sulfate was 747 +/- 502 ng/ml. Sodium excretion was correlated with hydroxy-triamterene sulfate levels in the controls (r = 0.81), but in the cirrhotics the diuretic response was correlated with basal sodium excretion (r = 0.86) and was not related to either triamterene or hydroxy-triamterene plasma concentrations. Our results indicate that chronic treatment with triamterene in patients with cirrhosis and ascites results in markedly elevated plasma levels, but these changes do not have a major influence on the magnitude of the diuretic response. 相似文献