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71.
Elif Şahin Horasan Gülden Ersöz Musa Göksu Feza Otag Ahmet Oner Kurt Sevim Karaçorlu Ali Kaya 《Mycopathologia》2010,170(4):263-268
Objectives
We aimed to asses possible clinically significant differences between C. parapsilosis and other candida species candidemia receiving care in the intensive care unit (ICU) setting.Methods
The study included 118 adult patients diagnosed as candidemia after admission to the ICU of a university hospital between January 2004 and December 2009. Data about demographic characteristics, underlying diseases, and risk factors for ICU-related candidemia were collected.Results
During the study period, 118 patients with candidemia were identified among 2,853 patients admitted into the ICU. Candidemia was seen in 41.4 cases per 1,000 ICU admissions. The overall incidence of candidemia in ICU patients during the study period was 2.09 per 1,000 hospital admissions. Of the isolates, 18.6% were C. albicans and 81.4% were C. non-albicans. The species most frequently isolated was C. parapsilosis (66.1%, 78/118). The distribution of other Candida spp. was as follows: 15 had C. tropicalis (12.7%) and 3 had C. glabrata (2.5%). By Statistical analysis, when patients with candidemia who had C. parapsilosis were compared with other Candida spp., the following factors were found to be significantly associated with C. parapsilosis fungemia; intravascular catheters (p = 0.008), malignity (p = 0.049) and age (p = 0.039). Relationship was found between C. tropicalis and hematologic malignancies (p = 0.001).Conclusions
When infections with a high mortality such as candidemia is suspected in critically ill patients, it is important to know local risk factors and epidemiological distributions of causative agents in selection of empirical and effective antifungal treatment. 相似文献72.
Courtney R. LaValle Kara M. George Elizabeth R. Sharlow John S. Lazo Peter Wipf Q. Jane Wang 《生物化学与生物物理学报:癌评论》2010
Protein kinase D is a novel family of serine/threonine kinases and diacylglycerol receptors that belongs to the calcium/calmodulin-dependent kinase superfamily. Evidence has established that specific PKD isoforms are dysregulated in several cancer types, and PKD involvement has been documented in a variety of cellular processes important to cancer development, including cell growth, apoptosis, motility, and angiogenesis. In light of this, there has been a recent surge in the development of novel chemical inhibitors of PKD. This review focuses on the potential of PKD as a chemotherapeutic target in cancer treatment and highlights important recent advances in the development of PKD inhibitors. 相似文献
73.
Prakash Peddi Charles W. Loftin Jennifer S. Dickey Jessica M. Hair Kara J. Burns Khaled Aziz Dave C. Francisco Mihalis I. Panayiotidis Olga A. Sedelnikova William M. Bonner Thomas A. Winters Alexandros G. Georgakilas 《Free radical biology & medicine》2010,48(10):1435-1443
DNA-dependent protein kinase (DNA-PK) is a key non-homologous-end-joining (NHEJ) nuclear serine/threonine protein kinase involved in various DNA metabolic and damage signaling pathways contributing to the maintenance of genomic stability and prevention of cancer. To examine the role of DNA-PK in processing of non-DSB clustered DNA damage, we have used three models of DNA-PK deficiency, i.e., chemical inactivation of its kinase activity by the novel inhibitors IC86621 and NU7026, knockdown and complete absence of the protein in human breast cancer (MCF-7) and glioblastoma cell lines (MO59-J/K). A compromised DNA-PK repair pathway led to the accumulation of clustered DNA lesions induced by γ-rays. Tumor cells lacking protein expression or with inhibited kinase activity showed a marked decrease in their ability to process oxidatively induced non-DSB clustered DNA lesions measured using a modified version of pulsed-field gel electrophoresis or single-cell gel electrophoresis (comet assay). In all cases, DNA-PK inactivation led to a higher level of lesion persistence even after 24–72 h of repair. We suggest a model in which DNA-PK deficiency affects the processing of these clusters first by compromising base excision repair and second by the presence of catalytically inactive DNA-PK inhibiting the efficient processing of these lesions owing to the failure of DNA-PK to disassociate from the DNA ends. The information rendered will be important for understanding not only cancer etiology in the presence of an NHEJ deficiency but also cancer treatments based on the induction of oxidative stress and inhibition of cluster repair. 相似文献
74.
Kara L. Vine Julie M. Locke John B. Bremner Stephen G. Pyne Marie Ranson 《Bioorganic & medicinal chemistry letters》2010,20(9):2908-2911
A urokinase targeting conjugate of 2′-deoxy-5-fluorouridine (5-FUdr) was synthesized and tested for tumor-cell selective cytotoxicity in vitro. The 5-FUdr prodrug 2′-deoxy-5-fluoro-3′-O-(3-carboxypropanoyl)uridine (5-FUdrsuccOH) containing an ester-labile succinate linker was attached to the specific urokinase inhibitor plasminogen activator inhibitor type II (PAI-2) and was found to preferentially kill urokinase-over expressing cancer cells. Up to 7 molecules of 5-FUdr were incorporated per PAI-2 molecule without affecting protein activity. This is the first time a small organic cytotoxin has been conjugated to PAI-2. 相似文献
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78.
The protective effects of melatonin, vitamin E, and selenium alone or in combination were tested against cadmium-induced oxidative
damage in rat testes. A total of 60 male rats were equally divided into five study groups, one of which acted as control receiving
subcutaneous injections of physiological saline. The remaining four groups were treated with subcutaneous injections of cadmium
chloride at a dose of 1 mg/kg weight. The first study group received no treatment. The second group was treated with a combination
of 60 mg/kg vitamin E and 1 mg/kg sodium selenite. Group 3 was treated with 10 mg/kg melatonin, and the fourth group received
a combination of vitamin E, sodium selenite, and melatonin at the doses mentioned above. After 1 month, the animals were killed,
and the testes were excised for histological inspection and determination of tissue malondialdehyde and the activity of superoxide
dismutase. The animals receiving no treatment showed significantly higher malondialdehyde levels and reduced activity of the
enzyme (p < 0.05). Treatment with antioxidants resulted in a significant reduction in malondialdehyde when compared to the nontreated
animals (p < 0.05) and an increase in the superoxide dismutase activity that was almost the same as the controls. The combination of
melatonin, vitamin E, and selenium appears to have the more profound effect against cadmium-induced testicular injury. 相似文献
79.
The present study was carried to evaluate the protective effects of melatonin alone and vitamin E with selenium combination
against high dose cadmium-induced oxidative stress in rats. The control group received subcutanous physiological saline. The
first study group administered cadmium chloride (CdCl2) by subcutaneous injection of dose of 1 mg/kg. The second study group administered cadmium plus vitamin E with selenium (1 mg/kg
sodium selenite with 60 mg/kg vitamin E); the third study group administered cadmium plus 10 mg/kg melatonin (MLT); the fourth
study group administered CdCl2 plus a combination of melatonin in addition to vitamin E and selenium for a month. Determination levels of plasma malondialdehyde
(MDA), glutathione peroxidase (GSH-Px), blood superoxide dismutase (SOD), creatinine alanine transaminase (ALT), aspartate
aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen (BUN), and urea were measured in serum. In only CdCl2 administered group, the MDA, creatinine, ALT, AST, ALP, and urea levels in the serum were significantly higher than the control
group (p < 0.05). Whereas in all other groups, this values were significantly lower than the only CdCl2 administered group (p < 0.05). Erythrocytes GSH-Px, serum SOD activities of only CdCl2 received group were significantly lower than the control group (p < 0.05). In conclusion, vitamin E + Se, melatonin and vitamin E, and Se, in addition to MLT combinations, had protective
effects against high dose cadmium-induced oxidative damage. 相似文献
80.
Ultrastructural changes in the kidneys of rats after acute cadmium exposure and the effects of exogenous metallothionein (MT)
were studied by transmission electron microscopy. Thirty-six adult Wistar rats were divided into three groups. Cadmium chloride
(CdCl2) (3.5 mg/kg/day) was injected subcutaneously in the first group. In the second group, 30 μmol/kg MT was administered in addition
to CdCl2. Control rats received 0.5 ml subcutaneous saline solution. Four rats from each group were killed on days 1, 3, 5, and 7
after administration of the compounds. Kidney tissues were taken and fixed in 2.5% glutaraldehyde solution for electron microscopic
observations. Tissue damage in kidney increased as time passed since the administration of CdCl2 in the first group. Degeneration in the proximal and distal tubules was observed. Increased apoptosis was seen in the proximal
tubules epithelium, especially on day 7. Peritubular capillaries became dilated, there was degeneration of the endothelial
cells, and the amount of intertubular collagen fibers was increased. On day 1, irregular microvilli in the proximal tubules,
deepening of the basal striations, and myelin figures; on day 3, multiple vesicular mitochondria and regions of edema around
tubules; on days 5 and 7, increased apoptotic cell in the proximal tubules and widened rough endoplasmic reticulum of the
endothelial cells of glomerular capillaries were observed. We observed that the structural alterations that increased depending
on the day of Cd administration decreased after exogenous MT administration, the dilation of the peritubular capillaries persisted,
and there were degenerated proximal tubules. It was established that cadmium chloride was toxic for kidney cortex and caused
structural damage. Exogenous MT partly prevents CdCl2-induced damage. 相似文献