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991.
Fixed-dose pegfilgrastim is safe and allows neutrophil recovery in patients with non-Hodgkin's lymphoma 总被引:2,自引:0,他引:2
George S Yunus F Case D Yang BB Hackett J Shogan JE Meza LA Neumann TA Liang BC 《Leukemia & lymphoma》2003,44(10):1691-1696
Twenty-nine patients with non-Hodgkin's lymphoma received a single subcutaneous injection of 6 mg pegfilgrastim approximately 24 h after the start of CHOP chemotherapy. The safety of pegfilgrastim in this patient population was determined by reports of adverse events. The pharmacokinetics of pegfilgrastim were characterized and the duration of grade 4 neutropenia, time to absolute neutrophil count (ANC) recovery to > or = 2.0 x 10(9)/l, neutrophil nadir, and incidence of febrile neutropenia were determined in the first 21-day chemotherapy cycle. The incidence of grade 4 neutropenia in cycle 1 was 43% with a mean (SD) duration of grade 4 neutropenia value of 1.0 (1.4) day. No apparent relationship between the duration of grade 4 neutropenia and body weight was observed. The median [quartiles] time to ANC recovery was 10 [9, 11] days. The incidence of febrile neutropenia was 11%. No unexpected adverse events were reported and no patient developed antibodies to pegfilgrastim. Serum concentration of pegfilgrastim reached a maximum (median [quartiles]) of 128 [58, 159] ng/ml at approximately 24 h after administration, and was followed by a second smaller peak (median [quartiles]) of 10.6 [3.0, 20.5] ng/ml at the time of the neutrophil nadir. After the second peak, concentration of pegfilgrastim declined linearly with a median terminal half-life of approximately 42 h. 相似文献
992.
Phaeochromocytoma associated with a de novo VHL mutation as form fruste of von Hippel-Lindau disease
Frenzel S Apel TW Heidemann PH Zerres K Neumann HP Dörr HG 《European journal of pediatrics》2001,160(7):421-424
Phaeochromocytomas usually occur sporadically but may be associated with dominant inherited cancer syndromes such as multiple
endocrine neoplasia type 2 (MEN 2), von Hippel-Lindau disease (VHL) and type 1 neurofibromatosis. We report on a boy presenting
at age 8 years with an isolated benign phaeochromocytoma of the left adrenal. Three years later a second adrenal phaeochromocytoma
was diagnosed on the right side and removed. His family history was negative. Genetic analysis did not show a mutation in
the MEN 2 susceptible proto-oncogene rearranged during transfection; however, we found a germline missense mutation in the
VHL gene (nucleotide 695 G to A transversion) which has been described only twice before in the literature. Both parents had
normal (wild type) VHL copies indicating that our patient had a de novo germline VHL mutation. Careful clinical evaluation
of the patient at 18 years did not reveal any other manifestations of VHL disease.
Conclusion Carriers of von Hippel-Lindau germline mutations can present with a form fruste of von Hippel-Lindau disease presenting initially
with unilateral phaeo-chromocytoma and therefore mutation analysis should be carried out.
Received: 21 June 2000 and in revised form: 18 February 2001 / Accepted: 20 February 2001 相似文献
993.
Farber disease is a rare, autosomal recessively inherited sphingolipid storage disorder due to the deficient activity of lysosomal acid ceramidase, leading to the accumulation of ceramide in cells and tissues. Here we report the identification of six novel mutations in the acid ceramidase gene causing Farber disease: three point mutations resulting in single amino acid substitutions, one intronic splice site mutation resulting in exon skipping, and two point mutations also leading to occasional or complete exon skipping. Of interest, these latter two mutations occurred in adjacent nucleotides and led to abnormal splicing of the same exon. Expression of the mutated acid ceramidase cDNAs in COS-1 cells and subsequent determination of acid ceramidase residual enzyme activity demonstrated that each of these mutations was the direct cause of the acid ceramidase deficiency in the respective patients. In contrast, two known polymorphisms had no effect on acid ceramidase activity. Metabolic labeling studies in fibroblasts of four patients showed that even though acid ceramidase precursor protein was synthesized in these individuals, rapid proteolysis of the mutated, mature acid ceramidase occurred within the lysosome. 相似文献
994.
Stickel F Baumüller HM Seitz K Vasilakis D Seitz G Seitz HK Schuppan D 《Journal of hepatology》2003,39(1):62-67
BACKGROUND/AIMS: Botanical drugs are widely used and often contain highly active compounds. Kava root (Piper methysticum rhizoma), used frequently in Europe as a remedy against anxiety, contains kavapyrones with sedative effects. Seven case reports suggested the development of hepatitis after the intake of Kava. METHODS: We analyzed 29 novel cases of hepatitis along with Kava ingestion which occurred between 1990 and 2002 in addition to the seven already published case reports using a clinical diagnostic scale established for adverse hepatic drug reactions. RESULTS: Hepatic necrosis or cholestatic hepatitis were noticed with both alcoholic and acetonic Kava extracts. The majority of the 29 patients and the additional seven published reports were women (27 females, nine males). Both the cumulative dose and the latency to when the hepatotoxic reaction emerged were highly variable. Nine patients developed fulminant liver failure, of which eight patients underwent liver transplantation. Three patients died, two following unsuccessful liver transplantation and one without. In all other patients, a complete recovery was noticed after the withdrawal of Kava. Pathophysiologically, both immunoallergic and idiosyncratic factors may be responsible. CONCLUSIONS: The present report emphasizes the potentially severe hepatotoxicity of Kava which has recently led to the retraction of Kava-containing drugs by the pharmacovigilance authorities in Germany. 相似文献
995.
996.
Gotthardt M Dirkmorfeld LM Wied MU Rinke A Béhé MP Schlieck A Höffken H Alfke H Joseph K Klose KJ Behr TM Arnold R 《Digestion》2003,68(2-3):80-85
AIM: Many studies describe the sensitivities and specificities of computed tomography (CT), magnetic resonance imaging (MRI), and somatostatin receptor scintigraphy (SRS) in patients with gastrointestinal neuroendocrine tumors (GNT). We performed a study to evaluate the influence of these techniques on the therapeutic management of patients with advanced stages of GNT. PATIENTS AND METHODS: The results of either CT/MRI scans or SRS were reviewed by two independent observers who decided on the therapy of a patient. They then had to determine whether the results of the complementary imaging modality would change the decision. The study design was a matched cross-over study with two groups matching in respect to tumor type, imaging modality known first to the observer, and number of patients. For further analysis, patients were divided into three subgroups dependent on tumor stage (group 1, without metastases, group 2, liver metastases, group 3, recurrent disease/extrahepatic metastases). RESULTS: 188 patients were included into the study. If SRS was known to the observers first, CT/MRI changed the therapeutic management in 16.2, 13.9 and 11.4% of the patients (subgroups 1-3). SRS changed the therapeutic management in 13.5, 12.5 and 10.3%. Overall, CT/MRI would have changed the management in 13.3% and SRS in 11.7% of the patients. CONCLUSION: Though the patients studied mainly suffered from already advanced stages of the disease, all imaging techniques change the therapeutic management to a comparable extent. Our results support the importance of combined imaging in the management of patients with GNT. 相似文献
997.
Klein IH Ligtenberg G Neumann J Oey PL Koomans HA Blankestijn PJ 《Journal of the American Society of Nephrology : JASN》2003,14(12):3239-3244
The hypothesis that in hypertensive patients with renal parenchymal disease sympathetic activity is "inappropriately" elevated and that this overactivity is a feature of renal disease and not of a reduced number of nephrons per se is addressed. Fifty seven patients with renal disease (various causes, no diabetes, all on antihypertensive medication) were studied, age range 18 to 62, creatinine clearance 10 to 114 ml/min per 1.73 m(2). Antihypertensives were stopped, but diuretics were allowed, to prevent overhydration. Matched control subjects were also studied. The effect of changes in fluid status was examined in seven patients while on and after stopping diuretics and in eight control subjects while on low- and high-sodium diet. Seven kidney donors were studied before and after unilateral nephrectomy. Sympathetic activity was quantified as muscle sympathetic nerve activity (MSNA) in the peroneal nerve. Mean arterial pressure, MSNA, and plasma renin activity were higher in patients than in control subjects, respectively (115 +/- 12 and 88 +/- 11 mmHg, 31 +/- 15 and 18 +/- 10 bursts/min, and 500 [20 to 6940] and 220 [40 to 980] fmol/L per s; P < 0.01 for all items). Extracellular fluid volume (bromide distribution) did not differ. Seven patients were studied again after stopping diuretics. MSNA decreased from 34 +/- 18 to 19 +/- 18 bursts/min (P < 0.01). Eight healthy subjects were studied during low- and high-sodium diet. MSNA was 26 +/- 12 and 13 +/- 7 bursts/min (P < 0.01). The curves relating extracellular fluid volume to MSNA were parallel in the two groups but shifted to a higher level of MSNA in the patients. In the kidney donors, creatinine clearance reduced by 25%, but MSNA was identical before and after donation. It is concluded that in hypertensive patients with renal parenchymal disease, sympathetic activity is inappropriately high for the volume status and that reduction of nephron number in itself does not influence sympathetic activity. 相似文献
998.
Vascular effects of cocoa rich in flavan-3-ols 总被引:6,自引:0,他引:6
999.
1000.
Balan S Leibovitz A Zila SO Ruth M Chana W Yassica B Rahel B Richard G Neumann E Blagman B Habot B 《The Journal of neuropsychiatry and clinical neurosciences》2003,15(3):363-366
Delirium is a common syndrome among hospitalized elderly patients. In humans, sleep and circadian rhythms are disturbed during delirium, and both are influenced by the hormone melatonin. This prompted us to investigate the relationship of the clinical subtypes of delirium: 1). hyperactive, 2). hypoactive, and 3). mixed, with melatonin, as reflected by a patient's urinary metabolite 6-SMT. Results support our hypothesis that urinary 6-SMT during delirium was higher in hypoactive and lower in hyperactive patients. Because this is the first time a biochemical parameter related to the clinical subtypes of delirium has been reported, further research on the link between melatonin and delirium is necessary. 相似文献