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71.
72.
Systematic screening for DNA sequence variation in the coding region of the human dopamine transporter gene (DAT1) 总被引:6,自引:0,他引:6
Grünhage F Schulze TG Müller DJ Lanczik M Franzek E Albus M Borrmann-Hassenbach M Knapp M Cichon S Maier W Rietschel M Propping P Nöthen MM 《Molecular psychiatry》2000,5(3):275-282
The dopamine transporter (DAT) plays a central role in dopaminergic neurotransmission in the human brain. Genetic association studies have used a variable number of tandem repeat (VNTR) polymorphism in the 3'-flanking region of the dopamine transporter gene (DAT1) to implicate the DAT in the development of various neuropsychiatric disorders. In this study, we have examined the possibility that a mutation exists in the coding region of the DAT1 gene which through linkage disequilibrium accounts for the observed associations. The complete coding region, as well as exon-intron boundaries, was screened in 91 unrelated individuals including 45 patients with bipolar affective disorder and 46 healthy control individuals by the means of single strand conformation analysis. Our findings suggest that the DAT1 gene is highly conserved since we detected only two rare missense substitutions (Ala559Val, Glu602Gly) and three silent mutations (242C/T, 1342A/G, and 1859C/T) in the whole coding region. Five sequence variants were observed in intronic sequences but none affects known splice sites. The lack of frequent variants of possible functional relevance indicates that genetic variation in the coding region of the DAT1 gene is not responsible for the previously observed associations with neuropsychiatric disorders. The two rare missense substitutions were found in single bipolar patients but not in controls. Investigation of the patients' families revealed independent segregation between the Ala559Val variant and affective disorder. The Glu602Gly variant was inherited by the proband from an affected father. It therefore remains possible that Glu602Gly may be a rare cause of bipolar affective disorder. 相似文献
73.
Serotonin transporter gene and schizophrenia: evidence for association/linkage disequilibrium in families with affected siblings 总被引:3,自引:0,他引:3
Hranilovic D Schwab SG Jernej B Knapp M Lerer B Albus M Rietschel M Kanyas K Borrmann M Lichtermann D Maier W Wildenauer DB 《Molecular psychiatry》2000,5(1):91-95
The serotonergic (5-HT) system has been implicated in the etiopathogenesis of psychoses. Since the 5-HT transporter plays an important role in regulation of 5-HT transmission, its gene can be considered as a candidate for vulnerability to psychiatric disorders. Two polymorphic sites of the 5-HT transporter gene-5-HTTLPR, a VNTR in the 5' regulatory region, and a VNTR in the second intron-were studied in a sample of 61 families with schizophrenia for transmission disequilibrium. Each family contained at least two siblings affected with schizophrenia or schizoaffective disorder (mainly schizophrenic). One hundred and thirty-nine affected offspring with parental information for genotyping, were available for analysis. No preferential transmission of either short or long alleles of the promoter polymorphism was observed. However, a transmission distortion was detected for alleles of the intronic VNTR polymorphism (chi2TDT max =14.33; P = 0.0002; corrected P value = 0.0003) resulting in more frequent than expected transmission of the 12 repeat allele. This finding adds additional evidence to the idea that the serotonergic system may be involved in development of psychoses. Molecular Psychiatry (2000) 5, 91-95. 相似文献
74.
Musholt TJ Musholt PB Petrich T Oetting G Knapp WH Klempnauer J 《World journal of surgery》2000,24(11):1409-1417
Hereditable predisposition to papillary thyroid carcinoma (PTC) and multinodular goiter (MNG) without evidence of an association
with other malignancies as a distinct entity was recognized only recently. A meta-review of the literature on familial PTC
(FPTC) was undertaken, and characteristics of families with frequent occurrence of PTC or MNG (or both) were summarized. A
database on thyroid cancer patients maintained in our institution was searched for potential FPTC families. Clinical examinations
were performed in 6 of 12 Hannover kindreds identified, and blood samples of all family members were collected for genetic
analyses. Clinical presentations and histopathologic features of the FPTC cases were compiled. Based on the FPTC meta-review
and own experience, predictive criteria to identify families at risk were developed: Exclusion criteria were previous radiation
exposure and coincidence with neoplasia syndromes. Primary criteria for susceptibility to FPTC are (1) PTC in two or more
first-degree relatives and (2) MNG in at least three first- or second-degree relatives of a PTC patient. Secondary criteria
are diagnosis in a patient younger than 33 years, multifocal or bilateral PTC, organ-exceeding tumor growth (T4), metastasis
(N1, M1), and familial accumulation of adolescent-onset thyroid disease. A hereditary predisposition to PTC is considered
if both primary criteria or one primary criterion plus three secondary criteria are present. Family history-taking is recommended
for all PTC patients to identify FPTC kindreds at risk. Blood relatives of FPTC index patients who harbor MNG should undergo
thorough and regular clinical screening. Suspicious lesions should prompt early surgical intervention. 相似文献
75.
Interest in the knowledge of salivary gland tumours is highlighted. A sample of 315 cases, collected over a period of 25 years in a busy pathology centre, is analysed both on total and individual aspects of tumours. The findings are compared to earlier works on the subject and also with contemporary literature.KEY WORDS: Pathological study, Salivary tumours 相似文献
76.
77.
Hyperbaric oxygenation induced tolerance against focal cerebral ischemia in mice is strain dependent 总被引:18,自引:0,他引:18
Prass K Wiegand F Schumann P Ahrens M Kapinya K Harms C Liao W Trendelenburg G Gertz K Moskowitz MA Knapp F Victorov IV Megow D Dirnagl U 《Brain research》2000,871(1):146-150
SV129 or C57BL/6 mice were exposed to hyperbaric oxygenation (HBO, 5 days, 1 h every day, 100% O(2) at 3 atm absolute). One day after the 5th HBO session focal cerebral ischemia was induced. In SV129 mice, HBO induced tolerance against permanent focal cerebral ischemia (n=42, mean infarct volume reduction 27%, P=0.001), but not against transient (30 or 60 min) focal cerebral ischemia. In the C57BL/6 strain of mice, HBO did not induce tolerance against focal cerebral ischemia, even when the duration of ischemia or the HBO protocol were modified. For the first time we demonstrate that HBO can induce tolerance to focal cerebral ischemia, but this effect is strain dependent. 相似文献
78.
Vitamin D receptor allele combinations influence genetic susceptibility to type 1 diabetes in Germans 总被引:17,自引:0,他引:17
Vitamin D has been shown to exert manifold immunomodulatory effects. Because type 1 diabetes is regarded to be immune-mediated and vitamin D prevents the development of diabetes in the NOD mouse, we investigated the role of the vitamin D receptor (VDR) gene as a candidate for type 1 diabetes susceptibility. A total of 152 Caucasian families with at least one affected offspring were genotyped for four VDR restriction-site polymorphisms (FokI, BsmI, ApaI, and TaqI). Whereas the BsmI, ApaI, and TaqI polymorphisms are in strong linkage disequilibrium with each other, no significant linkage disequilibrium with the FokI site was observed. Extended transmission disequilibrium testing (ETDT) was used to detect preferential transmission of allelic combinations to affected offspring. We found significant haplotype-wise ETDT results for the BsmI/ApaI/TaqI (chi2 = 18.886, df = 7, P = 0.0086), the BsmI/TaqI (chi2 = 8.373, df = 3, P = 0.0389), and theApaI/TaqI (chi2 = 17.182, df = 3, P = 0.0006) haplotypes. The "At" and "Bt" alleles confer an increased risk, whereas "AT" and "at" are protective. The combination with the strongest susceptibility was the "BAt" haplotype (64% transmitted, P = 0.0106). Analysis of the FokI site does not provide more information on susceptibility (FokI/BsmI/ApaI/TaqI [chi2 = 24.702, df = 15, P = 0.0541]). These findings suggest a linkage of VDR itself or a nearby gene with type 1 diabetes susceptibility in Germans, confirming respective observations previously made in Indian Asians. 相似文献
79.
Becker AJ Uckert S Stief CG Truss MC Machtens S Scheller F Knapp WH Hartmann U Jonas U 《The Journal of urology》2000,164(2):573-577
PURPOSE: Knowledge of the functional anatomy, hemodynamics, neurophysiology and pharmacology of penile erection has improved tremendously during the last 2 decades. However, only few in vivo studies on human peripheral neurotransmission have been carried out up until now. Therefore, we conducted a study to examine plasma levels of catecholamines norepinephrine (NE) and epinephrine (E) in the peripheral and cavernous blood of healthy men during penile flaccidity and in different phases of erection. MATERIALS AND METHODS: Blood samples were drawn simultaneously from the corpus cavernosum (CC) and the cubital vein (P) in 53 healthy volunteers with normal erectile function, in four different functional states of the cavernous erectile tissue (flaccidity = 1, tumescence = 2, rigidity = 3, detumescence = 4). Penile erections were induced by audiovisual and tactile stimulation and the plasma concentrations of NE and E were determined by means of a radioimmunoassay (RIA). RESULTS: A significant (p <0.001) reduction of NE in CC plasma was found from flaccidity (362 + or - 173 pg./ml.) to rigidity (248 + or - 122 pg./ml.), followed by an increase in the detumescence phase (336 + or - 199 pg./ml.), (p <0.001). In contrast, changes in NE levels in the peripheral plasma were less pronounced from 1P (202 + or - 102 pg./ml.) to 3P (229 + or - 118 pg./ml.), (p = 0.006) and from 3P to 4P (222 + or - 127 pg./ml.), respectively (p = 0.370). The most pronounced increase in cavernous E levels were observed from flaccidity (47 + or - 41 pg. /ml.) to tumescence (130 + or - 106 pg./ml.) (p <0.001). Cavernous E levels dropped significantly from 113 + or - 67 pg./ml. during rigidity to 76 + or - 57 pg./ml. + or - during detumescence (p <0.001). The course of peripheral plasma levels of E was similar to that in the cavernous blood. Mean peripheral E level was 69 + or - 55 pg./ml. in the state of penile flaccidity, reaching 98 + or - 78 pg./ml. in tumescence and 82 + or - 64 pg./ml. in rigidity (p <0.001), respectively, and finally decreasing to 62 + or - 46 pg./ml. in detumescence. CONCLUSION: Penile erection, based on the relaxation of cavernous and arterial smooth muscle, is accompanied by a significant reduction of NE in cavernous blood, while E levels rose in peripheral and cavernous blood during developing erection. 相似文献
80.