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41.
Stefan Silbernagl Katharina Völker William H. Dantzler 《Pflügers Archiv : European journal of physiology》1994,429(2):210-215
To investigate the fluxes of cationic amino acids beyond the proximal convolution, we micropunctured and microperfused superficial tubules of male Wistar rats in vivo et situ. In free-flow micropuncture experiments, the concentrations of endogenous L-arginine+, [Arg], and of intravenously infused L-homoarginine+, [HoArg], were determined by HPLC. Fluorescein isothiocyanatelabeled inulin was detected on-line in the same tubular fluid samples. To determine undirectional fluxes, radiolabeled Arg and inulin were (1) microperfused through short loops of Henle and (2) microinfused into different tubule segments to measure urinary recovery of the radiolabel. At a mean [Arg]plasma of 116 mol/l, [Arg] was 9.3 mol/l in the late proximal tubule (LPT), and 35.6 mol/l in the early distal tubule (EDT) corresponding to fractional deliveries (FD) of 0.055 in LPT and 0.078 in EDT. Fractional urinary excretion (FE) of Arg was 0.00033 (P<0.05 vs FDEDT). Infusion of HoArg (2.5 or 7.5 mol/min) led to respective mean [HoArg]plasma values of 1.44 and 3.73 mmol/l, and resulted in respective FDLPT values for HoArg of 0.23 and 0.53, respective FDEDT values of 0.29 and 0.41, and finally, respective FE values for HoArg of 0.25 and 0.58. When short loops of Henle were microperfused with 1 or 50 mmol/l [14C]Arg (+[3H]inulin), fractional recovery (FR) of 14C (relative to inulin) in the EDT was 0.13 and 0.36, respectively. During microinfusion of radiolabeled Arg (1 or 50 mmol/l) and inulin into LPT, the urinary FR of the radiolabel was 0.14, or 0.59, respectively. If 0.007, 1 or 50 mmol/l radiolabeled Arg were microinfused into EDT, the respective urinary FR of the radioactivity was 1.02, 1.10, or 1.01. Microperfusion of microinfusion of 1 mmol/l [14C]Arg plus 50 mmol/l HoArg resulted in a FREDT of 14C of 0.43 (loop, perfusion) and an FE for 14C of 0.69. Five conclusions can be drawn. First, cationic amino acids can enter and leave the lumen of short loops of Henle through specific carrier(s) at high rates, although, secondly, net transport is small or absent. Thus, medullary tubule cells can be supplied with Arg from the lumen of short loops of Henle for urea and nitric oxide production. Thirdly, the distal convolution of superficial nephrons and the collecting duct are not permeable to Arg. Thus, fourthly, the difference between FDEDT and urinary FE of Arg must be explained by an inter-nephron heterogeneity between deep and superficial nephrons. Finally, the process responsible for the different Arg handling in deep nephrons is not accessible to HoArg or, if so, it is saturated at millimolar concentrations. 相似文献
42.
Katharina Wenzel-Seifert Jürgen Ervens Roland Seifert 《Naunyn-Schmiedeberg's archives of pharmacology》1991,344(4):396-402
Summary The chemoattractants, N-formyl-L-methio-nyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe), complement C5a and platelet-activating factor (PAF), induce ß-glucuronidase release and aggregation and an increase in cytosolic Ca2+ [Ca2+]i in human neutrophils. We studied the roles of cAMP and cGMP in neutrophil avtivation, using their cell-permeant analogues, N6,2-O-dibutyryl adenosine 3:5-cyclic monophosphate (Bt2cAMP) and N2 ,2-O-dibutyryl guanosine 3:5-cyclic monophosphate (Bt2cGMP) and the NO-containing compounds, sodium nitroprusside (SNP), 3-morpholino-sydnonimine (SIN-1) and its prodrug, molsidomine (SIN-10). Bt2cAMP, Bt2cGMP, SIN-1 and SIN-10 but not SNP inhibited exocytosis induced by fMet-Leu-Phe. Superoxide dismutase potentiated the inhibitory effect of SIN-1. Bt2cGMP and SNP potentiated C5a-induced ß-glucuronidase release, Bt2cAMP, KCN, SIN-1 and SIN-10 being ineffective. KCN partially reversed the stimulatory effect of SNP, and in the presence of superoxide dismutase, SIN-1 potentiated C5a-induced exocytosis. PAF-induced ß-glucuronidase release was not affected by Bt2cAMP, Bt2cGMP, SNP and SIN-1. Bt2cGMP was more effective than Bt2cAMP to inhibit aggregation and the increase in [Ca2+]i induced by fet-Leu-Phe at submaximally effective concentrations. C5a-induced rises in [Ca2+]i were not affected by Bt2cAMP and Bt2cGMP. Bt2cAMP but not Bt2cGMP inhibited the effect of PAF at submaximally effective concentrations on [Ca2+]i. Our data suggest (I) that Bt2cGMP and Bt2cAMP differentially modulate neutrophil activation, that (II) NO-containing compounds partially mimick the effects of Bt2cGMP on exocytosis and that (III) cGMP plays an inhibitory role in fMet-Leu-Phe- and a stimulatory role in C5a-induced ß-glucuronidase release.
Send offprint requests to R. Seifert at the above address 相似文献
43.
Edward Chow Lori Holden Joel Rubenstein Monique Christakis Katharina Sixel Marjan Vidmar Joel Finkelstein Charles Hayter Andrew Loblaw Rebecca Wong Ewa Szumacher Cyril Danjoux 《Radiotherapy and oncology》2004,70(3):291-294
Twenty-five patients with osteolytic metastases had computed tomography (CT) scans before and 3 months after palliative radiotherapy. The median % density change following single 8 Gy, 20 Gy/5#, 30 Gy/10# were: 128 (range 98–255), 141 (79–342), and 145 (65–235), respectively. It is feasible to evaluate remineralization of osteolytic lesions with palliative radiotherapy. 相似文献
44.
Susanna Hegewisch-Becker Katharina Braun Markus Otte Aneta Corovic Djordje Atanackovic Axel Nierhaus Dieter K Hossfeld Klaus Pantel 《Clinical cancer research》2003,9(6):2079-2084
PURPOSE: Combining heat with antineoplastic drugs has produced evidence of antitumor synergism. An increasing number of trials are investigating whole body hyperthermia (WBH) in combination with chemotherapy in patients with advanced malignancies. Here we investigated whether the hyperdynamic state of the circulation as a consequence of WBH may stimulate dissemination of malignant cells. EXPERIMENTAL DESIGN: WBH in combination with chemotherapy was administered by a radiant heat device to 20 consecutive patients with advanced epithelial malignancies. One WBH session lasted for approximately 4 h (90 min heating time, 60 min plateau at 41.8 degrees C, and 60-80 min cooling). Peripheral blood was drawn before WBH treatment (baseline), at the end of the plateau (1 h), and 24 h and 48 h thereafter. After removal of leukocytes using anti-CD45 magnetic beads, circulating tumor cells were detected immunocytochemically using the monoclonal antibody A45-B/B3, which binds to a common epitope present on various cytokeratins. RESULTS: The method used to detect tumor cells in the peripheral blood proved to be specific and very sensitive (detection limit 1 tumor cell per 1.7 x 10(5) peripheral blood mononuclear cell). Before WBH, 6 of 20 patients had cyto-keratin-positive cells in their blood. A treatment-induced increase in the number of circulating tumor cells became statistically significant at 24 h after WBH (P = 0.043) and was detected in a total of 9 patients, 5 of whom had no detectable malignant cells at baseline. There was no evidence of a correlation between an increase in the number of circulating tumor cells and increased metastasis frequency. CONCLUSIONS: Our findings suggest that WBH might induce a temporary release of tumor cells into the circulation, but this spread appears to be clinically not significant in patients with advanced malignancies. 相似文献
45.
Expression of CEACAM6 in resectable colorectal cancer: a factor of independent prognostic significance. 总被引:2,自引:0,他引:2
Peter Jantscheff Luigi Terracciano Adam Lowy Katharina Glatz-Krieger Fritz Grunert Burkhard Micheel Jens Brümmer Urs Laffer Urs Metzger Richard Herrmann Christoph Rochlitz 《Journal of clinical oncology》2003,21(19):3638-3646
PURPOSE: CEACAM6, CEACAM1, and human carcinoembryonic antigen (CEA) are coexpressed in normal colorectal epithelia, but show deregulated expression in colorectal cancers (CRC). Upregulation of CEACAM6 expression in hyperplastic polyps and early adenomas represents one of the earliest observable molecular events leading to colorectal tumors. The aim of our study was to evaluate the prognostic relevance of CEACAM6, CEACAM1, and CEA tissue expression in patients with CRC. PATIENTS AND METHODS: Immunohistochemical analysis was carried out on tissue microarrays from 243 paraffin-embedded biopsies from a randomized controlled clinical trial (Swiss Group for Clinical Cancer Research [SAKK] 40/81) of adjuvant fluorouracil-based chemotherapy with CEACAM-specific monoclonal antibodies. The median follow-up was 8 years. Overall survival (OS) and disease-free survival (DFS) were calculated using Kaplan-Meier estimates and hazard ratios (HRs) estimated using Cox proportional hazards models. RESULTS: Tissue expression of CEACAM6, CEACAM1, and CEA was enhanced in 55%, 58%, and 94% of patients, respectively. Multivariate Cox analysis including sex, age, tumor site, stage, differentiation grade, treatment, and nodal status as covariates showed that CEACAM6 overexpression independently predicted poor OS (HR, 1.86; P =.0100) and DFS (HR, 2.00; P =.0028), whereas CEACAM1 or CEA were not significantly related to these outcomes. The data did not provide evidence for or against the hypothesis that the CEACAM6 effect on survival differs according to treatment. CONCLUSION: Expression of the cell adhesion molecule CEACAM6 in CRC is an independent prognostic factor allowing subdivision of patients into low- and high-risk groups. Whether CEACAM6 or CEA and CEACAM1 might be useful as predictive markers of chemotherapy benefit remains unclear. 相似文献
46.
47.
von Minckwitz G Darb-Esfahani S Loibl S Huober J Tesch H Solbach C Holms F Eidtmann H Dietrich K Just M Clemens MR Hanusch C Schrader I Henschen S Hoffmann G Tiemann K Diebold K Untch M Denkert C 《Breast cancer research and treatment》2012,132(3):863-870
Adjacent ductal carcinoma in situ (DCIS) is found in approximately 45% of invasive ductal carcinomas (IDC) of the breast. Pure DCIS overexpresses HER2 in approximately 45%. There is uncertainty whether adjacent DCIS impacts on the response to neoadjuvant chemotherapy and trastuzumab as well as whether HER2 expression in IDC component or adjacent DCIS changes throughout treatment. Core biopsies and surgical tissue from participants of the GeparQuattro study with HER2-positive IDC were centrally examined for the area of invasive ductal component and adjacent DCIS before and after receiving neoadjuvant anthracycline?Ctaxane?Ctrastuzumab containing chemotherapy. HER2 overexpression in IDC and adjacent DCIS was quantified separately by immunohistochemistry using the Ventana? automated staining system. Pathological complete response (pCR) was defined as no residual invasive or non-invasive tumor tissue. Fifty-nine (37.3%) of 158 IDCs presented with adjacent DCIS at diagnosis. These tumors showed lower regression grades than pure IDC (P?=?0.033). The presence of adjacent DCIS was an independent negative predictor of pCR [odds ratio 0.42 (95% CI 0.2?C0.9), P?=?0.027]. Adjacent DCIS area decreased from pre-treatment to surgery (r?=?0.205) with 30 (50.8%) IDCs with adjacent DCIS showing complete eradication of adjacent DCIS. HER2 status of adjacent DCIS was highly correlated with HER2 status of IDC component before (r?=?0.892) and after treatment (r?=?0.676). Degree of HER2 overexpression of the IDC component decreased in 16 (33.3%) out of 49 patients without a pCR. These 16 IDCs showed lower RGs compared to the 33 IDCs with unchanged HER2 expression (P?=?0.055). HER2-positive IDCs with adjacent DCIS is less responsive to neoadjuvant chemotherapy and trastuzumab compared to pure IDC. However, complete eradication of adjacent DCIS is frequently observed. HER2-overexpression of the invasive ductal component decreases in a subset of tumors, which showed less tumor regression. 相似文献
48.
49.
In this work, an attempt was made to improve the corrosion resistance of dilute Fe-Al alloys (1.0 mass% Al) by preheating treatment at 1073 K in H2 atmosphere. In comparison with pure Fe and unpreheated Fe-Al alloys, the resistance to oxidation at 673 K in pure O2 and to electrochemical corrosion in 5 wt.% NaCl solution is significantly improved for preheated Fe-Al alloys. This improvement is attributed to the formation of a 20 nm thin, but dense Al2O3 protective layer on the surface of preheated Fe-Al alloys. 相似文献
50.
Zhihao Wang Katharina S Goerlich Pengfei Xu Yue-jia Luo Andr Aleman 《Social cognitive and affective neuroscience》2022,17(10):912
Alexithymia is characterized by impairments in emotion processing, frequently linked to facial expressions of emotion. The eye-region conveys information necessary for emotion processing. It has been demonstrated that alexithymia is associated with reduced attention to the eyes, but little is known regarding the cognitive and electrophysiological mechanisms underlying emotive eye-region processing in alexithymia. Here, we recorded behavioral and electrophysiological responses of individuals with alexithymia (ALEX; n = 25) and individuals without alexithymia (NonALEX; n = 23) while they viewed intact and eyeless faces with angry and sad expressions during a dual-target rapid serial visual presentation task. Results showed different eye-region focuses and differentiating N1 responses between intact and eyeless faces to anger and sadness in NonALEX, but not in ALEX, suggesting deficient perceptual processing of the eye-region in alexithymia. Reduced eye-region focus and smaller differences in frontal alpha asymmetry in response to sadness between intact and eyeless faces were observed in ALEX than NonALEX, indicative of impaired affective processing of the eye-region in alexithymia. These findings highlight perceptual and affective abnormalities of emotive eye-region processing in alexithymia. Our results contribute to understanding the neuropsychopathology of alexithymia and alexithymia-related disorders. 相似文献