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101.
Gerhard Triebig Dieter Weltle Helmut Valentin 《International archives of occupational and environmental health》1984,53(3):189-204
Summary A cross-sectional study was performed in order to investigate the influence of chronic lead-exposure on the peripheral nervous system. We examined 148 male workers of a storage battery manufacturing plant, who had been exposed to lead metal and inorganic lead compounds for 1 to 28 years (mean 11 years). Fifteen workers with non-occupational risks of peripheral neuropathy (former diseases, alcohol abuse, medication) were excluded from the study. The investigation program comprised: case history, physical examination, analyses of blood- and urine-samples and determination of maximal motor, mixed and sensory conduction velocity (NCV) of the ulnar and median nerve of the right forearm. Objectively no worker showed any signs of health effects related to lead exposure. The Biological Monitoring included the determination of (1) Blood-lead level (Pb-B), (2) Free erythrocyte porphyrins (FEP), (3) -Aminolevulinic acid dehydratase (ALA-D) and (4) -Aminolevulinic acid in urine (ALA-U). Further time-weighted-average (TWA)-values of Pb-B were calculated on the basis of several determinations over the period 1975–1981. The following actual (TWA) median values resulted: Pb-B 53 g/dl (54 g/dl), ALA-U 5.6 mg/l (8.4 mg/l), FEP 2.0 mg/l (2.0 mg/l). The Biologischer Arbeitsstoff Toleranz Wert (BAT) of 70 g//dl for Pb-B was exceeded in 15 workers (11%), and of 15 mg/l for ALA-U in 30 cases (23%). In comparison with age-matched controls, the lead workers showed a mild slowing of NCV with mean values between 0.8 and 2.0 m/s. Multiple stepwise regression analyses revealed statistically significant correlations between the four NCV and age as well as Pb-B. There were better correlations by using TWA than actual data of Pb-B. Consideration of the results of the regression analyses, together with an evaluation of the individual neurophysiological status as a function of internal lead exposure, a dose-effect-relationship was found only in the case of Pb-B exceeding 70 g/dl. From our study it is concluded that chronic lead exposure resulting in blood-lead levels of below 70 g/dl is no occupational risk causing a functionally significant slowing of nerve conduction velocities.With Grants from the Deutsche Forschungsgemeinschaft, Bonn (Project no. Va 23/19-1) 相似文献
102.
Helmut Schrder Vanessa Cruz Muoz Marta Urquizu Rovira Victoria Valls Ibaez Josep-Maria Manresa Domínguez Gerard Ruiz Blanco Monserrat Urquizu Rovira Pere Toran Monserrat 《Nutrients》2021,13(6)
Increasing sugar-sweetened beverages (SSB) consumption and associated health impacts warrant health-policy action. We assessed associations of socioeconomic and lifestyle variables with adolescents’ consumption of regular soda (RSD), sport (SD), and energy (ED) drinks. Cross-sectional study of 3930 Spanish adolescents (2089 girls, 1841 boys) aged 13–18 years). We compared frequency of consuming each SSB type (European Food Safety Authority questionnaire) with sociodemographic and lifestyle variables (standardized questions). RSD, SD, and ED were consumed at least weekly by 72.7%, 32.3%, and 12.3% of participants, respectively, and more frequently (p < 0.001) by boys, compared to girls. Multivariate ordinal logistic regression showed inverse association between RSD, SD, and ED consumption and parental occupation-based socioeconomic status (p < 0.01). Daily smoking was associated (p < 0.001) with higher ED (OR 3.64, 95% CI 2.39–5.55) and RSD (OR 2.15, 95% CI 1.56–2.97) consumptions. SD intake was associated inversely with smoking (OR 0.60, 95% CI 0.40–0.89, p = 0.012) and directly with physical activity (OR 2.93, 95% CI 2.18–3.95, p < 0.001). School performance was lower among ED (OR 2.14, 95% CI, 1.37–3.35, p = 0.001) and RSD (OR 1.81, 95% CI 1.24–2.64, p = 0.002) consumers, compared to SD. Maleness and low socioeconomic status predicted SSB consumption. Smoking and low school performance were associated with higher ED and RSD intakes. 相似文献
103.
Rachel Wuerstlein Nadia Harbeck Eva-Maria Grischke Dirk Forstmeyer Raquel von Schumann Petra Krabisch Kerstin Lüdtke-Heckenkamp Andrea Stefek Oliver Stoetzer Andrea Grafe Gabriele Kaltenecker Helmut Forstbauer Doris Augustin Iris Schrader Joke Tio Ulrike Nitz Oleg Gluz Ronald E. Kates Monika Karla Graeser 《Breast care (Basel, Switzerland)》2021,16(1):50
BackgroundProtroca evaluated the efficacy and safety of primary and secondary prophylaxis of neutropenia with lipegfilgrastim (Lonquex®) in breast cancer patients receiving neoadjuvant or adjuvant chemotherapy (CT).Patients and MethodsOf the 255 patients enrolled, 248 patients were evaluable for the intent-to-treat (ITT) and 194 patients for the per-protocol set. Primary and secondary end points after lipegfilgrastim treatment were assessed.ResultsNine patients of the ITT set receiving lipegfilgrastim as primary prophylaxis (n = 222) had febrile neutropenia of grade 3–4 (5 patients) or infection of grade 3–4 (4 patients); 1/26 of those receiving secondary prophylaxis had an event. Dose reductions were performed in 9.5% of the patients. Postponement of cancer CT cycles for >3 days occurred in <15% of patients; 10.8% (92/851 AEs) and 8% (2/25 SAEs) of documented adverse events and serious adverse events, respectively, were related to lipegfilgrastim.ConclusionsApplication of lipegfilgrastim was effective as primary and secondary prophylaxis in the prevention of CT-induced neutropenia in breast cancer. 相似文献
104.
Pb2+ modulates the NMDA-receptor-channel complex 总被引:1,自引:1,他引:0
Vladimir Uteshev Dietrich Büsselberg Helmut L. Haas 《Naunyn-Schmiedeberg's archives of pharmacology》1993,347(2):209-213
Summary The actions of Pb2+ on NMDA channel currents of acutely dissociated hippocampal CA1- and CA3-neurones from adult rats activated by aspartate plus glycine (asp/gly) were examined. A fast reversible and a slow irreversible response to Pb2+ were found. Pb2+ applied simultaneously with asp/gly decreased an inward current. The threshold concentration was below 2 M, the current was reduced > 90% at concentrations over 100 M, The decrease of the asp/gly activated current showed no voltage dependence. Opening of NMDA channels was not necessary for Pb2+-action, as preincubation in 50 M Pb2+-containing external solution for several seconds dramatically reduced the response to asp/gly/Pb2+. This effect was reversed within 2 to 5 s of wash. Presence of Pb2+ or asp/Pb2+ or glycine/Pb2+ in the external solution did not prevent recovery of the NMDA receptor/channel complex from desensitization. Prolonged perfusion of a cell with the asp/gly/Pb2+-containing external solution resulted in an irreversible decrease of the asp/gly current, whereas the amplitude of the asp/gly/Pb2+ response did not change over the duration of an experiment. We conclude that Pb2+ modulates NMDA channel activity via interaction with the NMDA/glycine receptor: as a result the channel current decreases.Abbreviations NMDA
N-methyl-D-aspartate
- LTP
long-term potentiation
- AP5
2-amino-5-phosphonovalerate
- EGTA
ethylene glycol bis(-aminoethylether)-N,N,N,N-tetraacetic acid
- HEPES
4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid
Correspondence to H. L. Haas at the above address 相似文献
105.
Helmut Kreppel Franz -Xaver Reichl Ladislaus Szinicz Burckhard Fichtl Wolfgang Forth 《Archives of toxicology》1990,64(5):387-392
The efficacy ofdl-dimercaptopropanol (British Anti-Lewisite, BAL),dl-dimercaptopropanesulfonate (DMPS), and meso-dimercaptosuccinic acid (DMS A) was compared in reducing the acute As2O3 toxicity in mice. Mice were treated with a single equimolar dose of a dithiol compound (0.7 mmol/kg i.p.) 0.5 or 30 min after the s.c. injection of various doses of As2O3. Both DMPS and DMSA were significantly (p<0.05) more effective in mice treated 0.5 min after the poisoning if compared to BAL on an equimolar level. The highest potency ratio (PR) (LD50 with treatment/LD5o without treatment) was found in animals injected with DMSA (PR=8.6). The corresponding value for DMPS was 4.2, and for BAL 2.1, respectively. In animals treated 30 min after poisoning the efficacy of DMPS (PR = 2.6) was similar to the efficacy of DMSA 2.4, both being only slightly superior to BAL 2.O. DMPS and DMSA were found to be much less toxic than BAL. The LD50 of arsenic was 0.057 mmol/kg. The efficacy of BAL, DMPS, and DMSA in reducing the tissue content of arsenic following acute As2O3 poisoning was investigated in mice (n=6/group) and guinea pigs (n=3-4/group). The animals were injected s.c. with 0.043 mmol/kg As2O3 (containing a tracer dose of74As(III)). Thirty minutes later the antidotes were administered A were more effective in reducing the arsenic content of tissues than BAL. Moreover, BAL caused accumulation of the toxicant in the brain. It is concluded that the recommendation of BAL as drug of choice in acute arsenic poisoning needs to be carefully re-evaluated. 相似文献
106.
Helmut K. Wolf Matthias Spänle Marianne B. Müller Christian E. Elger Johannes Schramm Otmar D. Wiestler 《Acta neuropathologica》1994,88(4):313-319
Alterations of gamma aminobutyric acid (GABA)-mediated neurotransmission have been implicated in the pathogenesis of epilepsies. Here we examine the distribution of the GABAA receptor in the hippocampus of 78 surgical specimens from patients with chronic pharmacoresistant focal epilepsies. The receptor was localized immunohistochemically with the monoclonal antibody bd-24 which selectively recognizes the 1 subunit of the GABAA receptor. The results were compared with the receptor distribution of 28 normal hippocampal specimens obtained at autopsy. In the great majority of the surgical specimens a loss of GABAA receptor immunoreactivity was present in CA1 (92.3%), CA4 (78.2%), the dentate granular cell layer (70.5%) and the molecular layer of the dentate gyrus (65.4%). The subiculum revealed a normal staining pattern in all but 4 cases. In no instance did we observe an increase of immunoreactivity in any region or cell population. The decrease of GABAA receptor immunoreactivity was closely related to neuronal loss in the respective specimen and to Ammon's horn sclerosis. There was no correlation between GABAA receptor loss and the patient's age at surgery, duration of seizures, age at onset of seizures and to the presence or absence of secondary generalized tonic clonic seizures. The data suggest that the observed loss of GABAA receptor immunoreactivity is a secondary phenomenon rather than an event that is relevant for the pathogenesis of epileptic seizures. 相似文献
107.
Ronald Jabs Frank Kirchhoff Helmut Kettenmann Christian Steinhäuser 《Pflügers Archiv : European journal of physiology》1994,426(3-4):310-319
Glial cells in the CA1 stratum radiatum of the hippocampus of 9- to 12-day-old mice show intrinsic responses to glutamate due to the activation of -amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/ kainate receptors. In the present study we have focused on a subpopulation of the hippocampal glial cells, the complex cells, characterized by voltage-gated Na+ and K+ channels. Activation of glutamate receptors in these cells led to two types of responses, the activation of a cationic conductance, and a longer-lasting blockade of voltage-gated K+ channels. In particular, the transient (inactivating) component of the outwardly rectifying K+ current was diminished by kainate. Concomitantly, as described in Bergmann glial cells, kainate also elevated cytosolic Ca2+. This increase was due to an influx via the glutamate receptor itself. In contrast to Bergmann glial cells, the cytosolic Ca2+ increase was not a link to the K+ channel blockade, since the blockade occurred in the absence of the Ca2+ signal and, vice versa, an increase in cytosolic Ca2+ induced by ionomycin did not block the transient K+ current. We conclude that glutamate receptor activation leads to complex and variable changes in different types of glial cells; the functional importance of these changes is as yet unresolved. 相似文献
108.
Helmut Lindner 《Strahlentherapie und Onkologie》1999,175(1):44-45
Hintergrund
In den organbegrenzten Stadien des Prostatakarzinoms stehen die radikale Prostatektomie und die primÄre Radiotherapie als weitgehend gleichwertige Behandlungsverfahren zur Verfügung. Die Entscheidung wird von den Patienten deshalb oft aufgrund des jeweiligen Nebenwirkungsspektrums getroffen. Daten über diese Quoten liegen hÄufig nur von einzelnen Institutionen vor, differieren und sind nicht immer als Entscheidungshilfe geeignet. Metaanalysen haben sich andererseits bei vielen medizinischen Fragestellungen als hilfreiche Methode erwiesen.Methode
Zur Frage der erektilen Dysfunktion nach Radiotherapie und radikaler Prostatektomie haben die Autoren [4] eine sorgfÄltige Datenanalyse aus der verfügbaren Literatur durchgeführt. Aus etwa 600 Berichten wÄhlten sie anhand der Kriterien “Originalarbeiten seit 1970”, “bekannter prätherapeutischer sexueller Funktionszustand” und “keine gleichzeitige hormonelle Therapie” 40 Artikel aus, die solide Aussagen zum Thema erektile Dysfunktion lieferten.Ergebnisse
Nach der Radiotherapie betrug die Wahrscheinlichkeit 0,69, die prätherapeutische Erektionsfunktion zu erhalten, nach radikaler Prostatektomie (in den verschiedenen Varianten) 0,42. Der Unterschied war statistisch signifikant. Inkonsistenzen und die geringe Anzahl der Studien, die die genannten Kriterien überhaupt erfüllten, lie\en eine Auswertung anderer Variablen wie Patientenalter und Krankheitsstadien nicht zu.Schlu\folgerungen
Bei der Beurteilung des an und für sich evidenten Ergebnisses weisen die Autoren [4] aber auf SchwÄchen in den untersuchten Studien, wie oft ungenaue Definition der Begriffe “erektile Dysfunktion” und “Potenz”, differierende Angaben zum Zeitpunkt der Erfolgsbeurteilung, teilweises Fehlen der Altersangaben und des jeweiligen Krankheitsstadiums, hin und hoffen, da\ bei künftigen Berichten über neue Behandlungsmethoden, wie Kryotherapie, 3-D-geplante Radiotherapie, Brachytherapie u. a., wesentlich subtilere Angaben zu der wichtigen Nebenwirkung “erektile Dysfunktion” geliefert werden. 相似文献109.
L-701,324, a selective antagonist at the glycine site of the NMDA receptor, counteracts haloperidol-induced muscle rigidity in rats 总被引:1,自引:1,他引:0
J. Konieczny Krystyna Ossowska Gert Schulze Helmut Coper Stanislaw Wolfarth 《Psychopharmacology》1999,143(3):235-243
Rationale: It has recently been suggested that the overactivity of glutamatergic neurotransmission may contribute to the pathophysiology
of Parkinson’s disease. Therefore, a search for new compounds which block glutamatergic receptors and show antiparkinsonian
properties in animal models of this disease seems to be justified. Objective: The aim of this study was to determine whether L-701,324 [7-chloro-4-hydroxy-3(3-phenoxy) phenylquinoline-2-(H)-one], a selective
and full antagonist at the glycine site of the NMDA receptor, counteracts parkinsonian-like muscle rigidity and catalepsy
induced by haloperidol in rats. Methods: The muscle tone was measured as the resistance developed to passive flexion and extension of the hind limb. Electromyographic
(EMG) activity was additionally recorded in the gastrocnemius and tibialis anterior muscles. Results: L-701,324 (2.5–40 mg/kg IP) dose-dependently decreased the muscle tone enhanced by haloperidol (1–5 mg/kg IP). Likewise, the
haloperidol-enhanced resting EMG activity and the EMG reflex response to passive movements were diminished by lower and almost
abolished by higher doses of L-701,324. However, up to a dose of 20 mg/kg IP, L-701,324 did not influence haloperidol (0.5
mg/kg IP)-induced catalepsy. Moreover, L-701,324 (1.25–5 mg/kg IP) given alone or together with haloperidol (0.5–1 mg/kg IP)
disturbed rotarod performance. Gross observation of behaviour indicated that rats injected with L-701,324 in doses equal to
or higher than 5 mg/kg, alone or in combination with haloperidol, were markedly ataxic, i.e. rats showed signs of disturbed
balance and loss of control over their hind limbs. Conclusions: The present study suggests that L-701,324 exhibits a beneficial action in the animal model of parkinsonian rigidity, but not
that of parkinsonian akinesia. Nonetheless, this compound is not devoid of motor side-effects.
Received: 1 February 1998 / Final version: 20 October 1998 相似文献
110.
Summary Motor activity of rats was recorded following bilateral injections of GABA and the two GABA analogues gammahydroxybutyric acid (GHBA) and baclofen into the nucleus accumbens. GABA produced a shortlasting hypoactivity and this effect was potentiated by the GABA transaminase inhibitor aminooxyacetic acid (AOAA). More pronounced hypoactivities were caused by GHBA and baclofen. The hypoactivity was followed by hyperactivity after GHBA, baclofen and, to a small extent, after AOAA plus GABA. Systemic treatment with GHBA and GABA also suppressed motor activity and GHBA caused a subsequent hyperactivity. Small doses of GABA and particularly GHBA injected into the nucleus accumbens caused an increase in motor activity without the preceding decrease, especially when the rats were habituated to the environment. The effects appeared specific since no or only small changes in motor activity were induced by carnitine and betahydroxybutyric acid, structurally related to GABA and GHBA, respectively. Furthermore, the motor activity was stimulated by local treatment with the GABA receptor blocking agent picrotoxin, but not by strychnine or pentylenetetrazole. GHBA and GABA inhibited the apomorphine-induced activity of reserpine-treated rats indicating that these compounds stimulate GABA receptors beyond the dopamine synapses. The motor activity was depressed by GHBA and GABA given into the rostral and intermediate neostriatum and into the globus pallidus and, to a smaller extent, when given into the caudal neostriatum. The stimulatory effect of GHBA or picrotoxin was less, pronounced after local application to the globus pallidus or the neostriatum than when applied to the nucleus accumbens. The increased motor activity by GHBA, baclofen and GABA might be due to stimulation of GABA autoreceptors in the nucleus accumbens. The decreased motor activity might be evoked by stimulation of postsynaptic GABA receptors in the nucleus accumbens but a similar action in the corpus striatum might contribute.Part of the data was presented at the symposium on Interactions Among Putative Transmitters in the Brain held at the Mario Negri Institute, Milan, Italy on October 26–28, 1976 相似文献