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991.
992.
Barbara Teuchner Eduard Schmid Hanno Ulmer Waldemar Gottardi Markus Nagl 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2008,246(12):1723-1730
Background N-chlorotaurine (NCT), an endogenous mild antiseptic, is well-tolerated by application to the human conjunctiva and has been
shown to offer beneficial effects in infectious conjunctivitis. Animal tests revealed improved efficacy of a combination of
NCT with ammonium chloride in adenoviral conjunctivitis. The aim of this study was to evaluate the tolerability of NCT plus
ammonium chloride in the healthy rabbit and human eye.
Methods First, a tolerability study was performed in rabbits. In a blinded and randomized fashion, one eye was treated with the test
medication, the other one with 0.9% saline. Twenty-one animals (three per concentration) were treated with one drop every
2 hours for 6 days. Second, in two volunteers one drop of a defined concentration was applied to one eye every 15 min for
1 hour, saline to the control eye. Four different concentrations were tested on different days. Third, a double-blind, randomized
phase 1 study in 13 healthy volunteers was performed. One drop of 0.1% NCT plus 0.1% NH4Cl versus saline was applied every 15 min within the first hour, followed by four drops every 2 hours. This regimen was done
daily for 5 days.
Results In rabbits, no side effects were seen with 0.1% NCT plus 0.1% NH4Cl, while higher concentrations sometimes caused short-time and minimal conjunctival injection and secretion after dosing.
By 1% NCT plus 1% NH4Cl, these effects were moderate, but disappeared again without any detectable residues. In the pilot study with two volunteers,
treatment with 0.5% NCT plus 0.1% NH4Cl caused medium-scale eye burning for 30 seconds, while 0.1% NCT plus 0.1% NH4Cl was very well-tolerated, with no or minimal burning for a few seconds. In the subsequent phase 1 study, 0.1% NCT plus 0.1%
NH4Cl was well-tolerated by all subjects except for minimal eye burning for a few seconds after dropping. No objective signs
of eye changes could be detected in the human beings.
Conclusion The results of this study clearly demonstrate the good tolerability of a promising NCT formulation with improved activity. 相似文献
993.
Andrea Block Maria Rohde Ulrike Erben Markus Hammer Michael Hummel Katja Blunert Heinz-Peter Schultheiss Hans-Dieter Volk Michel Noutsias 《Medical science monitor》2008,14(5):BR88-BR95
BACKGROUND: The effects of different cell culture media on expansion efficiency and alterations in T-cell receptor V beta (TRBV) expression of in vitro expanded lymphocytes are not well established. MATERIAL/METHODS: Low numbers of CD3+ T cells from peripheral blood lymphocytes of healthy donors were subjected to polyclonal in vitro expansion in the presence of autologous CD3-depleted mononuclear cells as feeder cells (FCs) and their numbers and TRBV expressions were compared in media containing human (HS-RPMI) or fetal bovine serum (FBS-RPMI), Panserin413, or X-Vivo 15TM designed for lymphocyte culture. RESULTS: During three courses of restimulation within 28 days with CD3-antibody (OKT-3), IL-2, and initial CD3+, T-cell: FC ratios of 1:50 lowered to 1:5 and T cells expanded more than 1,000-fold in the media containing complete sera. Loss of cluster formation, associated with expansion failure, was only observed in cultures using synthetic media and resulted in only about 70-fold expansion. Whereas TRVB expression as determined by real-time PCR was substantially altered after 14 days of culture in X-Vivo 15, at day 28 only T cells from long-term culture in HS-RPMI presented the initial TRBV composition. CONCLUSIONS: Culture media have substantial impact on in vitro T-cell expansion. In the presence of FCs, medium containing human serum is superior to synthetic media and FBS-RPMI for long-term culture regarding T-cell number and TRBV repertoire. In contrast, the synthetic media Panserin413 and XVivo15 show lower expansion efficiency and reproducibility and, as RPMI1640+10%FBS, can contribute to overstimulation of certain TRBVs at advanced culture time points. 相似文献
994.
KvLQT1 (KCNQ1) is a very small conductance K+ channel distributed widely in epithelial and non-epithelial tissues. Its specific biophysical and pharmacological properties are determined by the regulatory subunits IsK (KCNE1) and MiRP2 (KCNE3). In epithelial cells of the inner ear, pancreas, and airways it interacts with IsK to conduct a voltage-gated and slowly activating K+ current. In the colon it coassembles with KCNE3 to conduct an instantaneous and constitutively active K+ current. In Cl- secretory epithelia, such as the colon and pancreas, this K+ channel provides the driving force for Cl- exit and is located in the basolateral membrane. In the inner ear it enables luminal secretion of K+ into the endolymphatic space. The functional relevance of KvLQT1 to epithelial function is revealed by blocking it pharmacologically or by studying animals with a genetic defect for it, which result in the breakdown of colonic Cl- secretion and endolymph production, respectively. KvLQT1 K+ channels are activated via cAMP or Ca2+ and inhibited by the chromanol 293B. Interaction with as yet unknown regulatory subunits may determine the properties of KvLQT1 in the rectal gland and other epithelial tissues in which KvLQT1 is not inhibited by chromanols. 相似文献
995.
Heinimaa ML 《Medicine, health care, and philosophy》2000,3(1):39-46
This study in the philosophy of psychiatrydeals with the concept `psychosis'. Methodologicallyit follows Wittgenstein's proposal
to `dissolve'philosophical problems by studying the actual use ofthe relevant concepts. Philosophical problemsconcerning both
identification of psychosis and themeaning of this concept are pointed out. The logicaldependencies between `psychosis' and
`understanding'and between `understanding' and the concept ofperson are demonstrated. Studying theinterdependence of these
concepts in the light ofthe actual uses of `madness' shows how the use of`psychosis' implies a radical loss of understanding.The
status and legitimacy of `psychosis' as a psychiatric concept is then demonstrated. 相似文献
996.
Influence of contrast-enhanced computed tomography on course and outcome in patients with acute pancreatitis 总被引:3,自引:0,他引:3
Uhl W Roggo A Kirschstein T Anghelacopoulos SE Gloor B Müller CA Malfertheiner P Büchler MW 《Pancreas》2002,24(2):191-197
INTRODUCTION: Many of the complications in severe acute pancreatitis result from the amplifying effects of microcirculatory disruption. Contrast medium may cause significant additional reductions of capillary flow, which has been shown to aggravate acute pancreatitis in experimental studies. AIM: To investigate the role of serial contrast-enhanced computed tomography (CECT) in patients with acute pancreatitis. METHODOLOGY: A retrospective analysis evaluated 302 patients with moderate to severe acute pancreatitis. Among these patients, 264 underwent CECT within 96 hours of the onset of symptoms and again during the course, but in 38 patients no serial CECT was performed. Outcome measurement was analyzed by comparison of hospital stay and mortality rate between the two patient groups. Influences of contrast medium on severity of disease were detected by monitoring complications during the course of treatment, C-reactive protein, and APACHE II score. RESULTS: The 1-month mortality rate was less in patients with CECT (6.4% versus 15.8%, p <0.05). There were no significant differences considering the incidence of additional complications, and hospital stay was not significantly longer (29 +/- 36 versus 19 +/- 13 days). C-reactive protein and APACHE II score had similar time courses. CONCLUSION: Contrast-enhanced computed tomography remains crucial in identifying patients with acute pancreatitis at high risk to develop necrosis of the pancreas and systemic complications. Contrast medium has been found to aggravate acute pancreatitis in animal models. As compared with the patient group without being exposed to contrast medium, however, this study did not show a deterioration of acute pancreatitis by administration of contrast medium in men. 相似文献
997.
998.
One-stage breast reduction and nipple-areolar reconstruction 总被引:1,自引:0,他引:1
The authors present an easily designed and accomplished technique of one-stage reduction mammaplasty and nipple-areolar reconstruction for patients with large or medium-size breasts and for patients missing the nipple-areolar complex. The technique has low inherent risks, and the symmetry of the breast is maintained to the maximum. In addition to the cosmetic improvement, using this technique benefits the patient further by avoiding postoperative corrections or adjustments. 相似文献
999.
Plonowski A Schally AV Letsch M Krupa M Hebert F Busto R Groot K Varga JL 《The Prostate》2002,52(3):173-182
BACKGROUND: Antagonists of growth hormone-releasing hormone (GHRH) such as JV-1-38 can inhibit androgen-independent prostate cancer directly by several mechanisms and/or indirectly by suppressing growth hormone/insulin-like growth factor-I (GH/IGF-I) axis. To shed more light on the mechanisms involved, the effects of JV-1-38 on PC-3 human prostate cancer were compared with those of somatostatin analog RC-160 in vivo and in vitro. METHODS: Nude mice bearing PC-3 tumors received JV-1-38 (20 microg), RC-160 (50 microg) or a combination of JV-1-38 and RC-160. The concentration of IGF-I in serum and the expression of mRNA for IGF-II and vascular endothelial growth factor (VEGF) in tumor tissue were investigated. RESULTS: In vivo, the final volume of PC-3 tumors treated with JV-1-38 was significantly lowered by 49% (P < 0.01), whereas RC-160 exerted only 30% inhibition (NS), compared with controls. Combined use of both compounds augmented tumor inhibition to 63% (P < 0.001). Serum IGF-I levels were decreased only in mice treated with RC-160. JV-1-38 suppressed mRNA for IGF-II in PC-3 tumors by 42%, whereas RC-160 alone or in combination with JV-1-38 caused a 65% reduction. JV-1-38 and RC-160 used as single drugs decreased the expression of VEGF by 50%, and their combination caused a 63% reduction. In vitro, JV-1-38 inhibited the proliferation of PC-3 cells by 39%. This effect could be partially reversed by addition of IGF-I to the serum-free medium. RC-160 alone did not affect the PC-3 cell growth in vitro, but in combination with JV-1-38 it augmented the antiproliferative effect of the GH-RH antagonist to 72%. Exposure to JV-1-38 in vitro reduced the expression of mRNA for IGF-II in PC-3 cells by 55% but did not change VEGF mRNA levels, whereas RC-160 had no effect. CONCLUSIONS: The antiproliferative effect of JV-1-38 was not associated with the suppression of serum IGF-I and was only partially correlated with the expression of IGF-II and VEGF in PC-3 tumors, suggesting that other mechanisms play a role in the antitumor action of GHRH antagonists. Nevertheless, the stronger inhibition of tumor growth after combined treatment with JV-1-38 and RC-160 indicates that the interference with multiple local stimulatory factors leads to an enhanced inhibition of prostate cancer. 相似文献
1000.
We aimed to establish a technically feasible, easily reproducible model of orthotopic adrenomedullary neoplasia. Male rats received adrenal injection of rat pheochromocytoma cells infected with the Escherichia coli gene for beta-galactosidase (lac Z). Each of 10 animals was perfused 7 or 24 days after tumor cell injection; 5 animals of each group were injected with cyclosporin. Animals without tumor cell injection served as controls. Tumor cells were identified and characterized in frozen sections by histochemical and immunohistochemical methods. Immunosuppressed animals had enlarged adrenals 7 days after tumor cell injection. In the rats without immunosuppression the adrenals seemed unaltered despite microscopic demonstration of tumor cells. After 24 days tumors had developed in all animals, weighing 50 times more than normal adrenals in animals with immunosuppression, and 9 times more in animals without immunosuppression. Intraadrenal catecholaminergic tumor cells could be identified by beta-galactosidase expression. No animal showed systemic spread. Generation of adrenomedullary neoplasia by intraadrenal pheochromocytoma cell transplantation is easily reproducible and technically feasible. This model allows simultaneous study of neoplastic and normal adrenal tissues (e.g., regarding their response to drugs intended for diagnostic and therapeutic purposes). The decreased tumor growth in animals without immunosuppression is presumably due to the high number of intraadrenal immunocompetent cells. 相似文献