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BACKGROUND: Gaining hemostatic control of vascular injuries sustained in combat using topical agents remains a challenge. We previously developed a new hemostatic agent consisting of a granular combination of a smectite mineral and a superabsorbent polymer (WoundStattrade mark; WS) which demonstrated the ability to stop high pressure bleeding. We have since modified WS to contain only the smectite mineral and compared the performance of WS to QuikClot'strade mark zeolite granules (QCG) in a lethal vascular injury model. METHODS: Fourteen (seven per group) anesthetized swine (35-44kg) had a lethal femoral artery injury produced by creating a 6mm arteriotomy in the vessel. After 45s of hemorrhage, animals were randomized to be treated with either WS or QCG for 3min. A second application was provided if hemostasis failed. Fluid resuscitation was begun at the time of application to achieve a mean arterial blood pressure of 65mmHg. Animals were observed for 120min or until death. Primary endpoints were survival, survival time, post-treatment blood loss, and resuscitation fluid volume. RESULTS: WS resulted in 100% survival to 120min. No animal in the QCG group survived (p=0.0005). Survival times for WS animals were significantly greater compared to QCG (p=0.0001). Post-treatment blood loss (p=0.0043) and post-resuscitation fluid volume (p=0.0043) was significantly less for animals treated with WS compared to QCG. CONCLUSION: WS consisting of just the smectite mineral was superior to QCG tested in this model. Additional study is warranted to determine its potential for use in combat and civilian trauma. 相似文献
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Hassan Awada Reda Z. Mahfouz Jibran Durrani Ashwin Kishtagari Deepa Jagadeesh Alan E. Lichtin Brian T. Hill Betty K. Hamilton Hetty E. Carraway Aziz Nazha Navneet S. Majhail Ronald Sobecks Valeria Visconte Matt Kalaycio Mikkael A. Sekeres Jaroslaw P. Maciejewski 《British journal of haematology》2020,189(2):318-322
T-cell large granular lymphocytic leukaemia (T-LGLL) is a chronic clonal lymphoproliferative disorder of cytotoxic T lymphocytes which commonly occurs in older patients and is often associated with autoimmune diseases. Among 246 patients with T-LGLL seen at our institution over the last 10 years, we encountered 15 cases following solid organ or haematopoietic stem cell transplantation. Here, we studied the clinical characterization of these cases and compared them to de novo T-LGLL. This experience represented a clear picture of the intricate nature of the disease manifestation and the complexities of several immune mechanisms triggering the clonal expansion. 相似文献
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Hassan Awada Reda Z. Mahfouz Ashwin Kishtagari Teodora Kuzmanovic Jibran Durrani Cassandra M. Kerr Bhumika J. Patel Valeria Visconte Tomas Radivoyevitch Alan Lichtin Hetty E. Carraway Jaroslaw P. Maciejewski Yogen Saunthararajah 《British journal of haematology》2020,188(6):924-929
The nucleoside analogue decitabine can deplete the epigenetic regulator DNA methyltransferase 1 (DNMT1), an effect that occurs, and is saturated at, low concentrations/doses. A reason to pursue this molecular-targeted effect instead of the DNA damage/cytotoxicity produced with high concentrations/doses, is that non-cytotoxic DNMT1-depletion can cytoreduce even p53-null myeloid malignancies while sparing normal haematopoiesis. We thus identified minimum doses of decitabine (0·1–0·2 mg/kg) that deplete DNMT1 without off-target anti-metabolite effects/cytotoxicity, and then administered these well-tolerated doses frequently 1–2X/week to increase S-phase dependent DNMT1-depletion, and used a Myeloid Malignancy Registry to evaluate long-term outcomes in 69 patients treated this way. Consistent with the scientific rationale, treatment was well-tolerated and durable responses were produced (~40%) in genetically heterogeneous disease and the very elderly. 相似文献
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Use of antiserum to neurotensin reveals a physiological role for the peptide in rat prolactin release. 下载免费PDF全文
E Vijayan R Carraway S E Leeman S M McCann 《Proceedings of the National Academy of Sciences of the United States of America》1988,85(24):9866-9869
Previous studies have indicated that the brain peptide neurotensin can stimulate prolactin release by direct action on the pituitary gland, whereas its action within the hypothalamus is inhibitory. The inhibitory action is mediated by the release of dopamine into the hypophyseal portal veins, which deliver the neurotransmitter to the anterior pituitary gland to inhibit prolactin release. Our experiments were done to evaluate the physiologic significance of these neurotensin actions by injecting the globulin fraction of highly specific neurotensin antiserum either intravenously or intraventricularly. Injection into the third ventricle of either 1 or 3 microliter of neurotensin antiserum significantly increased plasma prolactin concentrations in (i) ovariectomized and (ii) ovariectomized estrogen- and progesterone-primed rats within 1 hr of injection. The response was more pronounced in the ovariectomized than in the ovariectomized estrogen- and progesterone-treated animals and was dose related. Intraventricular injection of these doses of neurotensin antiserum also evoked elevations in plasma prolactin in intact males, which were significant but smaller in magnitude than those seen in female rats. To evaluate the effect of the antiserum on the pituitary directly, the antiserum was injected intravenously at a dose of 40 microliter, which was sufficient to block the blood pressure-lowering effect of neurotensin. After the intravenous injection of antiserum, a highly significant suppression of plasma prolactin occurred, detectable when first measured at 1 hr after injection in both ovariectomized and ovariectomized estrogen- and progesterone-treated animals; however, the intravenous injection of antiserum had no significant effect on the prolactin release in males. These data indicate the physiological significance of the hypothalamic inhibitory actions of neurotensin on prolactin release, which are probably mediated by its stimulation of dopamine release that in turn, inhibits prolactin secretion by the lactotropes. The direct stimulatory effect of the peptide on prolactin release after its presumed release into portal vessels also appears to be physiologically significant in female but not in male rats. 相似文献
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Lin Zhang Joseph JY Sung Jun Yu Siew C Ng Sunny H Wong Chi H Cho Simon SM Ng Francis KL Chan William KK Wu 《The Journal of pathology》2014,233(2):103-112
Helicobacter pylori and Epstein–Barr virus (EBV) account for roughly 80% and 10%, respectively, of gastric carcinomas worldwide. Autophagy is an evolutionarily conserved and intricately regulated cellular process that involves the sequestration of cytoplasmic proteins and organelles into double‐membrane autophagosomes that eventually fuse with lysosomes for degradation of the engulfed content. Emerging evidence indicates that xenophagy, a form of selective autophagy, plays a crucial role in the pathogenesis of H. pylori‐ and EBV‐induced gastric cancer. Xenophagy specifically recognizes intracellular H. pylori and EBV and physically targets these pathogens to the autophagosomal–lysosomal pathway for degradation. In this connection, H. pylori or EBV‐induced dysregulation of autophagy may be causally linked to gastric tumourigenesis and therefore can be exploited as therapeutic targets. This review will discuss how H. pylori and EBV infection activate autophagy and how these pathogens evade recognition and degradation by the autophagic pathway. Elucidating the molecular aspects of H. pylori‐ and EBV‐induced autophagy will help us better understand the pathogenesis of gastric cancer and promote the development of autophagy modulators as antimicrobial agents. Published by John Wiley & Sons, Ltd 相似文献
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C F Ferris M J Armstrong J K George C A Stevens R E Carraway S E Leeman 《Endocrinology》1985,116(3):1133-1138
We have previously reported that neurotensin (NT) is released from the small intestine and elevated in the hepatic-portal circulation in response to the perfusion of the small intestine with a micellar solution of oleic acid. In order to determine the minimum acyl chain length and whether the presence of a carboxylic acid is necessary for the stimulation of NT release, the small intestine of anesthetized rats was perfused with test solutions of fatty acids of 2-, 4-, 8-, or 18-carbons or fatty alcohols of 2-, 4-, or 8-carbons at a concentration of 1 mM prepared in 2.4 mM taurodeoxycholate in 0.9% NaCl. Blood samples, collected from the superior mesenteric vein immediately before the start of the test perfusion and at 15-min intervals thereafter, were extracted immediately and radioimmunoassayed for NT-like immunoreactivity (NTLI) with a C-terminal-directed antiserum. Perfusions of fatty acids with 4 or more carbons and alcohols of 2 or more carbons resulted in a significant elevation (P less than 0.05) in plasma levels of NTLI above the values obtained before the onset of perfusion. Perfusions with ethanol resulted in a value of 4.3 +/- 0.03 mg/dl (SEM) in blood from the superior mesenteric vein while there was no increase in ethanol levels in the peripheral circulation. Perfusion with taurodeoxycholate and 0.9% NaCl alone had no significant effect on plasma levels of the NTLI. In order to characterize the chemical nature of the elevated NTLI, plasma samples from animals perfused with test solution were collected, extracted, pooled, and subjected to HPLC. NT and its N-terminal metabolite, NT(1-8), were quantitated. NT was defined as material having the same retention time as synthetic NT standard and having comparable measurements using N- and C-terminal-directed antisera. Perfusions of fatty acids of four or more carbons and alcohols of two or more carbons resulted in a 2- to 4-fold increase of both NT and NT(1-8) levels in plasma. It is particularly interesting that perfusion with ethanol (2-carbons) causes an elevation in plasma NT, because perfusion with acetic acid (2-carbons) does not increase NTLI. The fact that perfusion of ethanol is effective in releasing intestinal NT suggests that NT may mediate some of the biological effects observed after the consumption of alcohol. 相似文献
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