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991.
Combined 1p/19q loss in oligodendroglial tumors: predictive or prognostic biomarker? 总被引:2,自引:0,他引:2
Michael Weller Hilmar Berger Christian Hartmann Johannes Schramm Manfred Westphal Matthias Simon Roland Goldbrunner Dietmar Krex Joachim P Steinbach Christoph B Ostertag Markus Loeffler Torsten Pietsch Andreas von Deimling 《Clinical cancer research》2007,13(23):6933-6937
PURPOSE: The combined loss of genetic material on chromosomes 1p and 19q is strongly associated with favorable outcome in patients with WHO grade 3 anaplastic oligodendroglial tumors. The prognostic value of 1p/19q loss in WHO grade 2 oligodendroglial tumors is less well defined. Importantly, the possible effect of combined 1p/19q loss has not been studied in patients who were not treated with radiotherapy or chemotherapy. EXPERIMENTAL DESIGN: Seventy-six patients with oligodendroglioma (n = 33), oligoastrocytoma (n = 30), anaplastic oligodendroglioma (n = 6), or anaplastic oligoastrocytoma (n = 7) were identified who had not received radiotherapy or chemotherapy after their first operation until the end of follow-up or until the first progression and had tissue for 1p/19q status available. 1p/19q status was assessed by multiplex ligation-dependent probe amplification. RESULTS: After a median follow-up of 3.8 years, progressive disease was documented in 34 patients. The estimated median progression-free survival was 4.6 years. Fifty-eight of the 76 patients had a combined loss of 1p and 19q. The absence or presence of combined 1p/19q loss was not prognostic for progression-free survival using multivariate adjustment for histology, extent of resection, and gender. CONCLUSIONS: Combined 1p/19q loss is not a sensitive prognostic biomarker in patients with oligodendroglial tumors who do not receive radiotherapy or chemotherapy. The gene products lost as a consequence of this codeletion may include mediators of resistance to genotoxic therapies. Alternatively, 1p/19q loss might be an early oncogenic lesion promoting the formation of glial neoplasms, which retain high sensitivity to genotoxic stress. 相似文献
992.
Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression. 总被引:2,自引:0,他引:2
Thomas E Schlaepfer Michael X Cohen Caroline Frick Markus Kosel Daniela Brodesser Nikolai Axmacher Alexius Young Joe Martina Kreft Doris Lenartz Volker Sturm 《Neuropsychopharmacology》2008,33(2):368-377
Deep brain stimulation (DBS) to different sites allows interfering with dysfunctional network function implicated in major depression. Because a prominent clinical feature of depression is anhedonia--the inability to experience pleasure from previously pleasurable activities--and because there is clear evidence of dysfunctions of the reward system in depression, DBS to the nucleus accumbens might offer a new possibility to target depressive symptomatology in otherwise treatment-resistant depression. Three patients suffering from extremely resistant forms of depression, who did not respond to pharmacotherapy, psychotherapy, and electroconvulsive therapy, were implanted with bilateral DBS electrodes in the nucleus accumbens. Stimulation parameters were modified in a double-blind manner, and clinical ratings were assessed at each modification. Additionally, brain metabolism was assessed 1 week before and 1 week after stimulation onset. Clinical ratings improved in all three patients when the stimulator was on, and worsened in all three patients when the stimulator was turned off. Effects were observable immediately, and no side effects occurred in any of the patients. Using FDG-PET, significant changes in brain metabolism as a function of the stimulation in fronto-striatal networks were observed. No unwanted effects of DBS other than those directly related to the surgical procedure (eg pain at sites of implantation) were observed. Dysfunctions of the reward system--in which the nucleus accumbens is a key structure--are implicated in the neurobiology of major depression and might be responsible for impaired reward processing, as evidenced by the symptom of anhedonia. These preliminary findings suggest that DBS to the nucleus accumbens might be a hypothesis-guided approach for refractory major depression. 相似文献
993.
Markus Vogt Maria Vertzoni Klaus Kunath Christos Reppas Jennifer B Dressman 《European journal of pharmaceutics and biopharmaceutics》2008,68(2):338-345
The oral bioavailability of EMD 57033, a calcium sensitizing agent with poor solubility, was compared in dogs using four solid dosage form formulation approaches: a physical blend of the drug with excipients, micronization of the drug, preparation of coground mixtures and spray-drying of the drug from a nanocrystalline suspension. The formulations contained generally accepted excipients such as lactose, hydroxypropylmethyl cellulose and sodium lauryl sulphate in usual quantities. Drug micronization and cogrinding was realized by a jet-milling technique. Nanoparticles were created by media milling using a bead mill. All formulations were administered orally as dry powders in hard gelatine capsules. While micronization increased the absolute bioavailability of the solid drug significantly compared to crude material (from nondetectable to 20%), cogrinding with specific excipients was able to almost double this improvement (up to 39%). With an absolute bioavailability of 26%, spray-dried nanoparticular EMD 57033 failed to show the superior bioavailability that had been anticipated from in vitro data. The control solution prepared with cyclodextrin was shown to have an absolute bioavailability of 57% (vs. i.v. infusion). It was concluded that cogrinding can be a useful tool to improve the bioavailability of poorly soluble drugs from a solid dosage form format. 相似文献
994.
Markus Frlich 《Econometrics Journal》2007,10(2):359-407
Summary Propensity score matching is frequently used for estimating average treatment effects. Its applicability, however, is not confined to treatment evaluation. In this paper, it is shown that propensity score matching does not hinge on a selection on observables assumption and can be used to estimate not only adjusted means but also their distributions, even with non‐i.i.d. sampling. Propensity score matching is used to analyze the gender wage gap among graduates in the UK. It is found that subject of degree contributes substantially to explaining the gender wage gap, particularly at higher quantiles of the wage distribution. 相似文献
995.
Safwan Rihawi Markus Frentz Jakob Becker Martin Reim Norbert Franz Schrage 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2007,245(10):1507-1513
Background Immediate rescue intervention for chemical and thermal eye burns can save the victim’s sight. We studied the anterior chamber
pH changes immediately after ex vivo eye burn to investigate the effects of immediate and delayed intervention.
Methods Twenty three enucleated pigs eyes were burnt with 500 μl 2 mol NaOH for 20 s using a cylinder with a diameter of 10 mm. The
corneas were rinsed in groups with 1015 ml ordinary tap water at a flow rate of 1.125 ml/s for 15 minutes immediately after
burning (n = 6), and after a delay of 20, 40, and 60 s (n = 5, 3 and 4 respectively). One group of eyes was not rinsed (n = 5). The intraocular pH was defined at the start as ‘min pH’ and the end as ‘max pH’(ΔpH = max pH-min pH).
Results The intraocular pH increased sharply in the untreated eyes from a min pH of 6.76 ± 0.55 to a max pH of 11.85 ± 0.24, yielding
a ΔpH of 5.08. The difference between the timepoint at which the pH began to increase and the speed of change was significantly
different between the unrinsed and rinsed eyes, and there was an inverse correlation between this and the time at which rinsing
started (p < 0.001). The best results were achieved in eyes rinsed immediately after burning (p < 0.001). The pH in the eyes not rinsed immediately increased rapidly, and in all groups in which rinsing was delayed the
max pH was markedly higher (p = 0.093).
Conclusions Immediate emergency rinsing is essential in eye burn victims. Appropriate rinsing solutions and treatment facilities in the
form of rinsing stations where chemical burns may occur must be available at the workplace. Tap water is also effective as
a rinsing solution.
Presentation The results were the subject of a short oral presentation at the 104th DOG Annual Meeting 2006 in Berlin. 相似文献
996.
Johannes Beckmann Franz Kock Markus Tingart Juergen Goetz Joachim Grifka Jens Schaumburger 《Central European Journal of Medicine》2008,3(3):377-379
We present a case of pseudarthrosis in a patient suffering from polyostotic fibrous dysplasia of the right part of the body
that was successfully treated with bone morphogenetic protein. Pseudarthrosis occurred after proximal femoral shaft fracture
due to a motorcycle accident initially treated by intramedullary nailing. After revision, the patient was treated by pseudarthrosis
debridement and grafting of bone morphogenetic protein-7/osteogenic protein-1, resulting in callus formation that allowed
indolent full weight-bearing after 6 weeks. The underlying disease as well as the described treatment is discussed. 相似文献
997.
998.
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
999.
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
1000.
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