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排序方式: 共有7132条查询结果,搜索用时 422 毫秒
61.
Julian Stürznickel Tim Rolvien Alena Delsmann Sebastian Butscheidt Florian Barvencik Stefan Mundlos Thorsten Schinke Uwe Kornak Michael Amling Ralf Oheim 《Journal of bone and mineral research》2021,36(2):271-282
Reduced bone mineral density (BMD; ie, Z-score ≤−2.0) occurring at a young age (ie, premenopausal women and men <50 years) in the absence of secondary osteoporosis is considered early-onset osteoporosis (EOOP). Mutations affecting the WNT signaling pathway are of special interest because of their key role in bone mass regulation. Here, we analyzed the effects of relevant LRP5 and LRP6 variants on the clinical phenotype, bone turnover, BMD, and bone microarchitecture. After exclusion of secondary osteoporosis, EOOP patients (n = 372) were genotyped by gene panel sequencing, and segregation analysis of variants in LRP5/LRP6 was performed. The clinical assessment included the evaluation of bone turnover parameters, BMD by dual-energy X-ray absorptiometry, and microarchitecture via high-resolution peripheral quantitative computed tomography (HR-pQCT). In 50 individuals (31 EOOP index patients, 19 family members), relevant variants affecting LRP5 or LRP6 were detected (42 LRP5 and 8 LRP6 variants), including 10 novel variants. Seventeen variants were classified as disease causing, 14 were variants of unknown significance, and 19 were BMD-associated single-nucleotide polymorphisms (SNPs). One patient harbored compound heterozygous LRP5 mutations causing osteoporosis-pseudoglioma syndrome. Fractures were reported in 37 of 50 individuals, consisting of vertebral (18 of 50) and peripheral (29 of 50) fractures. Low bone formation was revealed in all individuals. A Z-score ≤−2.0 was detected in 31 of 50 individuals, and values at the spine were significantly lower than those at the hip (−2.1 ± 1.3 versus −1.6 ± 0.8; p = .003). HR-pQCT analysis (n = 34) showed impaired microarchitecture in trabecular and cortical compartments. Significant differences regarding the clinical phenotype were detectable between index patients and family members but not between different variant classes. Relevant variants in LRP5 and LRP6 contribute to EOOP in a substantial number of individuals, leading to a high number of fractures, low bone formation, reduced Z-scores, and impaired microarchitecture. This detailed skeletal characterization improves the interpretation of known and novel LRP5 and LRP6 variants. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). 相似文献
62.
Notfall + Rettungsmedizin - Das akute Koronarsyndrom ist der häufigste Grund für einen Rettungsdiensteinsatz in Deutschland. So resultieren in etwa 20–25 % aller Einsätze... 相似文献
63.
Klaus Hager Uwe Machein Stephan Krieger Dieter Platt Gerhard Seefried Joachim Bauer 《Neurobiology of aging》1994,15(6):771-772
In the present study, interleukin-6(IL-6) and several acute phase proteins were measured in healthy participants (23–87 years of age). A linear correlation between IL-6 and age was established with an increase of 0.016 pg/ml(00.004) per year of life. Whereas CRP remained below 0.5 mg/dl in all participants, an increase with age for fibrinogen and an inverse relation for albumin as well as transferrin were obtained. However, the increase of IL-6 did not correlate with any of these changes. IL-6 associated diseases may therefore occur more often with advancing age, but in healthy participants IL-6 does not explain the changing plasma protein pattern resembling that of an acute phase reaction. 相似文献
64.
Walther Seiler Hermann Wetzel Andreas Hillert Günter Schöllnhammer Michael Langer Uwe Barlage Christoph Hiemke 《Psychopharmacology》1994,116(4):457-463
Pharmacokinetics and bioavailability of benperidol were determined in 13 schizophrenic patients after acute administration of 6 mg benperidol as an intravenous (i.v.) bolus injection, orally as liquid, and orally as tablets using a partially randomized cross-over design. Drug plasma levels were determined by high performance liquid chromatography with electrochemical detection and subjected to model independent pharmacokinetic analyses. After i.v. dosing the geometric means (mean-g) were 3.2 min for the distribution half-life, 5.80 h for the elimination half-life (t
1/2), 4.21 l/kg for the distribution volume, 7.50 h for the mean residence time (MRT), and 0.50 l/(h*kg) for the clearance. After oral administration as liquid and as tablet mean-g data for the time lag until the first appearance of measurable plasma concentrations were 0.33 and 1.1 h, mean-g
t
1/2 values were 5.5 and 4.7 h, respectively, mean-g t
max data were 1.0 h and 2.7 h, mean-g MRT values were 8.44 and 8.84 h, and mean-g C
max
maxvalues were 10.2 and 7.3 ng/ml. Differences between liquid and tablet administration were statistically significant for time lag,t
max, andC
max. Mean-g absolute bioavailabilities were computed as 48.6% after liquid and 40.2% after tablet administration respectively. All parameters studied exhibited large intersubject variation. The plasma concentrations of the presumed metabolite reduced benperidol were found to be very low. 相似文献
65.
Robert M. Mader Harald Zilg Otto Schlappack Günther G. Steger Martina Baur Bertold Greifenberg Uwe Heberle Christian Dittrich 《Cancer chemotherapy and pharmacology》1995,37(1-2):91-96
Improved quality of life has gained importance over shortly lasting remissions in yet incurable metastatic breast cancer. Fractionation of drug administration is one of the possible approaches to reduce the concentration-dependent toxicity of anthracyclines. We evaluated the pharmacokinetics of 4-O-tetrahydropyranyladriamycin (THP-ADM) under weekly administration in patients with advanced breast cancer (dose escalation, from 20 to 27 mg/m2 THP-ADM). The concentration-time curves of THP-ADM in plasma were best described by an open three-compartment model [half-life of the first disposition phase (t1/2), 3.15 min; terminal elimination half-life (t
1/2), 13.9 h] with a mean area under the curve (AUC) of 12.2 ng h ml–1mg–1m–2, resulting in a mean plasma clearance of 86.91 h–1m–2. Metabolism included the formation of Adriamycin (ADM), Adriamycinol (ADM-OH), 13-dihydro-4-O-tetrahydropyranyladriamycin (THP-OH), 7-deoxyadriamycinone (7H-ADn), and 7-deoxy-13-dihydroadrimycinone (7H-ADn-OH), with maximal plasma concentrations ranging from 2.8 to 5.5 ng/ml. The mean total amount of cytotoxic anthracyclines excreted into urine, mainly as the parent drug, was 5% of the delivered dose. ADM and ADM-OH, but not the parent drug, were observed in urine at up to 4 weeks after the last therapeutic cycle. There was a significant correlation between the leukocyte nadir under therapy and the AUC of ADM-OH (r=0.800,P<0.05). Since no shift in the plasma kinetics was observed from the first to the sixth cycle, the favorable ratio of the AUCs of THP-ADM and ADM after fractionation of THP-ADM suggests lower toxic side effects attributable to ADM. This hypothesis was confirmed in a clinical study, where no severe cardiotoxicity and only mild alopecia were observed in 19 patients. Thus, pharmacokinetics studies might be helpful in both individualization of therapy with THP-ADM and optimization of the administration schedule. 相似文献
66.
MRI findings in Hirayama’s disease: flexion-induced cervical myelopathy or intrinsic motor neuron disease? 总被引:6,自引:0,他引:6
Schröder R Keller E Flacke S Schmidt S Pohl C Klockgether T Schlegel U 《Journal of neurology》1999,246(11):1069-1074
Hirayama’s disease is a benign juvenile form of focal amyotrophy affecting the upper limbs. Previous studies have suggested
that the disorder is a neck flexion induced cervical myelopathy. We report clinical and magnetic resonance imaging findings
in nine patients with Hirayama’s disease. Cervical imaging of seven patients revealed spinal cord changes consisting of focal
atrophy and foci of signal alterations. On neck flexion a forward movement and mild reduction in the anteroposterior diameter
of the lower cervical cord against the vertebral bodies was noted in affected individuals as well as in five normal controls.
In contrast to earlier reports, none of our patients showed complete obliteration of the posterior subarachnoid space. Measurement
of the anteroposterior spinal cord diameter in each vertebral segment (C4–C7) revealed no significant differences in the degree
of spinal cord flattening between the two groups. Furthermore, two of our patients had significant degenerative changes in
the cervical spine (disc herniation, retrospondylosis) contralateral to the clinically affected side. These degenerative changes
resulted in a marked cord compression on neck flexion but were not associated with ipsilateral clinical abnormalities or spinal
cord alterations. Our results argue against a flexion-induced cervical myelopathy and support the view that Hirayama’s disease
is an intrinsic motor neuron disease.
Received: 15 March 1999 Received in revised form: 25 May 1999 Accepted: 1 June 1999 相似文献
67.
Seitz RJ Knorr U Azari NP Herzog H Freund HJ 《Restorative neurology and neuroscience》1999,14(1):25-33
Recovery of finger movements after hemiparetic stroke has been shown to involve sensorimotor brain areas in perilesional and remote locations. Hand use, however, critically depends on visual guidance in such patients with stroke lesions in the middle cerebral artery territory. Using regional cerebral blood flow measurements, we wished to identify interrelated brain areas that are engaged in relation to manual activity in seven patients after their first hemiparetic brain infarction. During the blind-folded performance of sequential finger movements, the patients differed significantly from healthy controls (n = 7) by the recruitment of a predominantly contralesional network involving visual cortical areas, prefrontal cortex, thalamus, hippocampus, and cerebellum. Greater expression of this cortical-subcortical network correlated with a more severe sensorimotor deficit in the acute stage after stroke reflecting its role for post-stroke recovery. Patients also differed from controls on a lesion-related pattern expressed during rest. A third differentiating pattern involved the ipsilesional supplementary motor area and the contralesional premotor cortex. Our results suggest that post-stroke recovery form impaired sensorimotor integration utilizes crossmodal plasticity of a visual network. 相似文献
68.
Important inroads are being made into understanding the pathophysiology of diarrhea. Clear understanding of key mechanisms
should suggest new approaches to combat disease. Exciting developments are occurring in terms of super-ORS solutions, particularly
with the promise of short chained glucose polymers and glutamine. Perhaps the most important development is the prospect of
a good rotavirus vaccine being available before the end of the decade.
Chronic diarrhea seems to be on the increase globally, probably because of the success of ORS. The mechanisms that lead to
mucosal injury are elusive, and therapy still largely supportive and empiric. Celiac disease continues to be a puzzle, because
of the uncomfortable feeling that a majority of cases may be missed because of atypical presentations. The successful use
of long term parenteral nutrition has allowed survival and better charaterization of cases that otherwise would have perished
as ‘lethal protracted diarrhea’. Microvillus inclusion disease may be the commonest congenital secretory diarrhea. The role
of the recently reported high prevalence of glucoamlase deficiency may be important. Lastly, attention to micronutrients,
particularly low vitamin A and probably zinc may prove to be important in prevention and amelioration of diarrhea and growth
failure. 相似文献
69.
Detlev von Cramon Uwe Schuri 《European archives of psychiatry and clinical neuroscience》1980,229(1):45-52
Summary The Vigilance Scale (VS) is a 12-step additive scale (Guttman scale) that allows assessment of the behavioral deficit in the unconscious state and the state of clouding of consciousness. Despite restrictions on its applicability, which are discussed in detail, the VS seems to be a useful measuring device that indicates the level of brain function a patient with a disturbance of consciousness can actually attain. There are two categories of scale errors to be found, the first being caused by various instrumental disorders, i.e., severe motor deficits, the second resulting from the probabilistic approach of the VS to a Guttman scale. 相似文献
70.
Vaccination of patients with advanced ovarian carcinoma with the anti-idiotype ACA125: immunological response and survival (phase Ib/II). 总被引:7,自引:0,他引:7
Silke Reinartz Siegmund K?hler Harald Schlebusch Karl Krista Patrick Giffels Kirsten Renke Jens Huober Volker M?bus Rolf Kreienberg Andreas DuBois Paul Sabbatini Uwe Wagner 《Clinical cancer research》2004,10(5):1580-1587
PURPOSE: A Phase I/IIb multicenter study was conducted to evaluate the safety and immunogenicity of the anti-idiotypic antibody vaccine ACA125 that functionally imitates the tumor antigen CA125 in 119 patients with advanced ovarian carcinoma. A preliminary report on the initial 42 patients demonstrated safety and immunogenicity. EXPERIMENTAL DESIGN: Using the complete intention-to-treat population (n = 119) who received a mean of 9.7 ACA125 applications, survival was analyzed with respect to immunological responses. RESULTS: In 81 patients (68.1%), a specific anti-anti-idiotypic antibody (Ab3) response could be induced. Additionally, the development of CA125-specific antibodies (Ab1') and antibody-dependent cell-mediated cytotoxicity of CA125-positive tumor cells was observed in 50.4% and 26.9% of patients, respectively. The median survival of all patients was 19.4 months (range, 0.5-56.1 months). Ab3-positive patients showed a significantly longer survival (median, 23.4 months; P < 0.0001) as compared with Ab3-negative patients (median, 4.9 months). A positive Ab3 response remained associated with longer survival when controlling for other prognostic factors including FIGO (International Federation of Gynecologists and Obstetricians) stage, response to and type of first-line chemotherapy, number of previous treatments, or concomitant antitumor therapy. With regard to safety, repeated vaccination was well tolerated. No serious adverse events related to the application of ACA125 occurred. CONCLUSIONS: Although the uncontrolled design of this study prevents definitive conclusions with respect to subgroups, the data support a relationship between Ab3 response and survival time. Thus, the need for further randomized, controlled clinical trials to establish efficacy of the vaccine ACA125 seems to be indicated. 相似文献