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21.
The interaction between clonidine and opiate receptor antagonists on arterial blood pressure (BP) and heart rate were examined in normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). In conscious SHR, the hypotension and bradycardia caused by clonidine, 5 micrograms/kg iv, were significantly attenuated by naltrexone, 2 mg/kg ip. In urethane-anesthetized SHR, the reduction in mean BP and heart rate in response to 5 nmol clonidine microinjected into the nucleus of the solitary tract (NTS), were similarly inhibited after intra-NTS microinjection of 100 ng DL-naloxone but not after the same dose of D-naloxone. Neonatal treatment of SHR by monosodium glutamate (MSG) markedly reduced the beta-endorphin (BE) but not the leucin-enkephalin content of the arcuate nucleus and the NTS. MSG treatment did not affect the basal BP of these animals, but significantly reduced the hypotensive effect of clonidine and eliminated its susceptibility to opiate antagonists in both conscious and anesthetized SHR. In conscious and anesthetized WKY, the cardiovascular effects of clonidine were smaller than in SHR and were unaffected by naloxone or naltrexone. Neonatal treatment of WKY with MSG reduced the BE content of the arcuate nucleus but not of the NTS. MSG treatment of WKY did not influence either basal BP or the cardiovascular effects of clonidine, and the latter remained unaffected by opiate antagonists. These findings support the hypothesis that in SHR, but not in WKY, the centrally mediated cardiovascular effects of clonidine are partially mediated by the release of a BE-like opioid. They also strongly suggest that the site of both the release and the action of this opioid is in the NTS. 相似文献
22.
Elena Thomaidou Liran Horev Deborah Jotkowitz Mariana Zamir Arieh Ingber Claes D. Enk Vered Molho-Pessach 《The American journal of tropical medicine and hygiene》2015,93(4):770-773
Cutaneous leishmaniasis (CL) is diverse in its clinical presentation but usually demonstrates an erythematous, infiltrated, ulcerated, and crusted papule or nodule in exposed areas of the body. Rare clinical features have been reported including lymphatic dissemination, usually with subcutaneous nodules along lymphatic channels. Herein, we present six patients suffering from Old World CL with lymphatic dissemination characterized by sporotrichoid subcutaneous nodules along the lymphatic channels draining the primary lesion. Patients'' history, clinical and laboratory findings were collected and summarized. Lymphatic dissemination of CL in our patients manifested as subcutaneous nodules without epidermal involvement within the axis of lymphatic drainage toward the regional lymph node, at times accompanied by regional lymphadenopathy. In all patients, the lymphatic dissemination was not present at initial diagnosis of CL, appearing only after local (topical or intralesional) treatment was initiated. In three patients, the subcutaneous nodules resolved without systemic treatment. Lymphatic dissemination of Old World CL is not uncommon and may possibly be triggered by local treatment. It should be recognized by dermatologists, especially those working in endemic areas. Systemic treatment may be not necessary since spontaneous resolution may occur.Old World cutaneous leishmaniasis (CL) is diverse in its clinical presentation and outcome. The disease spectrum is governed by an interplay between the parasite and the immuno-inflammatory response of the host. The typical clinical presentation of CL is an erythematous, infiltrated, ulcerated, and crusted papule or nodule on any region of the body, with frequent involvement of exposed areas, especially the face and limbs. Lesions heal slowly over a period of months.1 Although CL often resolves spontaneously, it can result in severe disfiguration. Treatment is usually initiated to hasten healing and prevent scarring.2Old World CL is endemic in Israel and was attributed in the past almost exclusively to Leishmania (Leishmania) major, confined to rural areas of the Negev Desert in southern Israel. Over the last decade, CL due to Leishmania tropica has been increasingly reported in the Judean Desert in central Israel, as well as in northern Israel. Leishmania tropica is often more resistant to treatment and heals more slowly than L. major infections.3Lymphatic dissemination of CL is uncommon but has been reported, usually with dermal or subcutaneous nodules along lymphatic vessels draining the region of the primary lesion.4–7 Herein, we present six cases of CL with subcutaneous sporotrichoid dissemination after local treatment of the primary lesion, probably caused by lymphatic spread of the parasites. The sporotrichoid dissemination was characterized by deep subcutaneous nodules without any sign of epidermal involvement.The demographic, clinical, and laboratory data of the patients are summarized in 8 performed on tissue obtained from primary lesions (patients 4 and 5) or from subcutaneous nodules (patient 6) confirmed L. tropica infection. Regional lymphadenopathy was noted in two patients (patients 2 and 3). In patients 3 and 6, a biopsy from the subcutaneous nodules established the presence of a deep granulomatous process with Leishmania bodies. After the occurrence of subcutaneous nodules, three patients were treated with intravenous sodium stibogluconate (patient 1, 3, and 4), or with sodium stibogluconate injected directly into the primary cutaneous lesion alone (patient 6) or into both the cutaneous lesion and the subcutaneous nodule (patient 5). The patients experienced total resolution of the primary lesions, the subcutaneous nodules, as well as regional lymphadenopathy. On the parents'' request, intralesional injections of pentostam were terminated after a single treatment in patient 2. The primary lesion eventually healed with a scar and the subcutaneous nodules spontaneously regressed within a few weeks.
Open in a separate windowF = female; M = male; ITS1-PCR = internal transcribed spacer 1 polymerase chain reaction.Open in a separate windowFigure 1.(A) A 5-cm infiltrated and ulcerated erythematous plaque over the right forearm in patient 1. (B) Lymphatic dissemination without epidermal involvement in patient 1. (C) A 3-cm ulcerated erythematous plaque on the right lower forehead and two 5-mm soft and mobile subcutaneous nodules on the right cheek and right upper eyelid with overlying faint pink discoloration in patient 2.Open in a separate windowFigure 2.Histopathological findings from a subcutaneous nodule on the left forearm in patient 3: inflammatory infiltrate composed of lymphocytes, histiocytes, and abundant macrophages; round or oval basophilic structures can be seen consistent with Leishmania amastigotes (hematoxylin and eosin, original magnification ×600).Open in a separate windowFigure 3.(A) Infiltrated erythematous, ulcerated plaques on the right cheek, right upper lip, and angle of mouth with a painless subcutaneous cord extending from the right angle of the mouth to the right chin in patient 4. (B) A 2-cm erythematous ulcer on nose tip with subcutaneous nodes extending proximally in patient 5. (C) A 1.5-cm ulcer on the dorsal aspect of the middle phalanx of the fourth finger in patient 6. (D) Subcutaneous nodules on the dorsum of the right hand, proximal to the finger lesion in patient 6.Sporotrichoid dissemination is characterized by the development of secondary lesions, often associated with lymphangitis that progresses along dermal and subcutaneous lymphatics.The exact prevalence of Old World sporotrichoid CL is unknown but ranges between 10% and 19% of affected individuals in previous reports.6,7 The majority of reported sporotrichoid CL cases were shown to be caused by L. major,4,7 although L. tropica has also been implicated. The prevalence of this phenomenon may be species dependent but there are no data comparing rates of sporotrichoid CL among various species. Akilov and others9 in their classification of Old World CL also described this pattern of local spread of CL. They regard the sporotrichoid subcutaneous nodules as a form of lymphatic dissemination of the parasite and describe three clinical patterns: 1) subcutaneous nodules in proximity to the primary lesion, 2) dilated palpable lymphatic vessels in the form of a “beaded cord,” and 3) regional lymphadenitis,9 all seen in our case series.Lymphatic dissemination in our patients manifested in the form of subcutaneous nodules without the typical surface changes noted in primary CL lesions (scaling, crusts, erosions, or ulcers). This was confirmed by the biopsy specimens taken from patients 3 and 6 showing the lack of epidermal and superficial dermal involvement. The nodules were either located within the axis of lymphatic drainage toward the regional lymph node or were accompanied by regional lymphadenopathy. The presence of numerous Leishmania bodies in biopsy specimens of patients 3 and 6 supports the notion that the subcutaneous nodules represent metastases of the parasitic infection.In all our patients, the lymphatic dissemination was absent at initial diagnosis of CL and appeared only after local treatment was initiated. In the 261 patients who attended our Leishmania clinic over the last 2 years, sporotrichoid dissemination was observed only in the six herein reported cases (2.3%), suggesting that local treatment may trigger for this phenomenon, although a proof of cause and effect is currently lacking. Previous reports in the literature also suggest that lymphatic dissemination may be evoked by antiparasitic therapy, especially the use of local irritants and local injections.7,9 It has been shown that intralesional sodium stibogluconate induces an inflammatory response at the site of injection as well as tissue damage,10 which may activate lymphatic drainage and result in parasitic dissemination. Therefore, we hypothesize that the tissue damage caused by local treatment triggers the spread of the parasites into the subcutis and lymphatic vessels. Large prospective studies in endemic areas, where ITS1-PCR can be performed for parasite speciation using a large prospective randomized controlled trial, are needed to prove the causative relationship raised here between local treatment and lymphatic spread of CL.Pentavalent antimonials such as sodium stibogluconate and meglumine antimoniate either systemically or intralesionally have been used to treat sporotrichoid CL.4,7 In three patients (patients 2, 5, and 6), we observed disappearance of the subcutaneous nodules following the resolution of the primary lesions, without initiating systemic treatment. Therefore, we suggest that initiation of systemic treatment in cases of lymphatic dissemination of Old World CL should be guided by the response of the primary lesion to the local treatment. Although no information is available, this may not be true for New World CL, where concern for mucosal disease exists.Lymphatic dissemination of Old World CL is uncommon. This pattern of lymphatic and subcutaneous spread of CL, possibly triggered by local treatment, should be recognized by dermatologists, especially those working in endemic areas. Awareness to this phenomenon will prevent unnecessary workup to investigate the nature of the subcutaneous lesions. 相似文献
Table 1
Demographic, clinical, and laboratory findingsCases | Sex | Age (years) | Geographic region | Presenting symptoms | Initial treatment before appearance of subcutaneous nodules | Morphology and location of subcutaneous nodules | Regional lymphadenopathy | Investigations | Treatment with intravenous sodium stibogluconate | Response to treatment |
---|---|---|---|---|---|---|---|---|---|---|
1 | M | 16 | Negev Desert | 8-month history of an infiltrated and ulcerated erythematous plaque on right forearm | Paromomycin ointment | Subcutaneous painless cord extending proximally in a linear pattern from the right antecubital fossa toward the axilla (Figure 1A, ,BB) | No | Smear: positive for amastigotes | Yes | Flattening of the indurated plaque and disappearance of the subcutaneous cord |
Doppler ultrasound: infiltration of lymphatic vessels | ||||||||||
2 | M | 1.8 | Negev Desert | 6-month history of an ulcerated erythematous plaque on the right lower forehead | Paromomycin ointment and intralesional sodium stibogluconate | Two 5-mm soft and mobile subcutaneous nodules on the right cheek and right upper eyelid with overlying faint pink discoloration (Figure 1C and andC),C), appeared a few weeks after the treatment with intralesional sodium stibogluconate | Yes (cervical) | Smear: positive for amastigotes | No | Subcutaneous nodules spontaneously regressed and the ulcerated plaque healed leaving a scar |
Ultrasound: nondiagnostic | ||||||||||
3 | F | 16 | Judean Desert | 1-year history of two ulcerated erythematous plaques on right and left forearms | Paromomycin ointment and four treatment with intralesional sodium stibogluconate once weekly | Numerous 2-mm subcutaneous nodules above the primary lesions up to the armpit in both upper extremities | Yes (axillary) | Smear: positive for amastigotes | Yes | Flattening of the primary lesions and disappearance of the subcutaneous nodules |
Ultrasound: nondiagnostic. | ||||||||||
Biopsy (from a subcutaneous nodule on the left arm):normal epidermis and dermis, an epithelioid granuloma with plasma cells and abundance of Leishmania bodies was noted in the subcutaneous fat (Figure 2 | ||||||||||
4 | M | 9 | Judean Desert | 10-month history of infiltrated erythematous, ulcerated plaques on the right cheek, right upper lip, angle of mouth, and left forearm | Two intralesional treatments with sodium stibogluconate | Subcutaneous cord extending from the right angle of the mouth to the right aspect of the jaw (Figure 3A) | No | Smear: positive for amastigotes | Yes | Resolution of the subcutaneous cord and flattening of the plaques on face and forearm |
ITS1-PCR: tissue from a primary lesion was positive for Leishmania tropica | ||||||||||
5 | F | 7 | Judean Desert | 2 months history of erosive erythematous plaques at the tip of the nose, upper lip and five papules on right arm | Three intralesional treatments with sodium stibogluconate | Two subcutaneous nodules, without overlying erythema, proximal to the nose lesion | No | Smear: positive for amastigotes | No | Continued treatment with intralesional sodium stibogluconate with resolution of the lesions, as well as the subcutaneous nodules |
ITS1-PCR: tissue from a primary lesion was positive for L. tropica | ||||||||||
6 | M | 17 | Judean Desert | 3 months history of an ulcerated plaque on the middle phalanx of the fourth finger and an erythematous erosive plaque on right upper arm | One intralesional treatment with sodium stibogluconate | Two subcutaneous nodules on the dorsal aspect of the right hand, proximal to the lesion on fourth finger (Figure 3C, ,DD) | No | Biopsy (from a subcutaneous nodule): profound granulomatous process in the deep dermis with necrosis in the form of palisading granulomas. Suspicious Leishmania bodies were noticed within necrotic areas | No | Continued treatment with intralesional sodium stibogluconate with resolution of the lesions, as well as the subcutaneous nodules |
ITS1-PCR: tissue from a subcutaneous nodule was positive for L. tropica |
23.
Role of leisure-time physical activity in nonalcoholic fatty liver disease: a population-based study
Zelber-Sagi S Nitzan-Kaluski D Goldsmith R Webb M Zvibel I Goldiner I Blendis L Halpern Z Oren R 《Hepatology (Baltimore, Md.)》2008,48(6):1791-1798
Physical activity (PA) is commonly recommended for nonalchoholic fatty liver disease (NAFLD) patients. However, there is limited evidence on the independent role of PA in NAFLD. The aim of this study was to examine the association between PA and NAFLD. We conducted a cross-sectional study of a subsample (n = 375) of the Israeli National Health and Nutrition Survey. Exclusion criteria were any known etiology for liver disease. Participants underwent an abdominal ultrasound examination; biochemical tests, including leptin, adiponectin, and resistin; and the noninvasive biomarker SteatoTest and anthropometric evaluations. A semiquantitative food frequency questionnaire and a detailed PA questionnaire were administered. Three hundred forty-nine patients (52.7% men, 30.9% primary NAFLD) were included. The NAFLD group engaged in less aerobic, resistance, or other kinds of PA (P = 0.03). The SteatoTest was significantly lower among subjects engaging in any PA or resistance PA at least once a week (P = 0.01). PA at least once a week in all categories was associated with a reduced risk for abdominal obesity. Adjusting for sex, engaging in any kind of sports (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.44-0.96 per 1 standard deviation increment in PA score) and resistance exercise (OR 0.61, 95% CI 0.38-0.85) were inversely associated with NAFLD. These associations remained unchanged after adjusting for homeostasis model assessment, most nutritional factors, adiponectin, and resistin. Only the association with resistance PA remained significant with further adjustment for body mass index (OR 0.61, 95% CI 0.44-0.85). Adding leptin or waist circumference to the model eliminated the statistical significance. Conclusion: Habitual leisure-time PA, especially anaerobic, may play a protective role in NAFLD. This association appears to be mediated by a reduced rate of abdominal obesity. 相似文献
24.
Revital Kariv Moshe Leshno Anat Beth-Or Hana Strul Laurie Blendis Ehud Kokia Dina Noff Shira Zelber-Sagie Bracha Sheinberg Ran Oren Zamir Halpern 《Liver international》2006,26(4):445-450
BACKGROUND: The upper normal limit (ULN) of serum alanine-aminotrasferase (ALT) normal range was recently challenged, because patients diagnosed with liver diseases may have 'normal' or near-'normal' ALT levels, and because possible modulators are often ignored in determining normal range. AIM: To estimate the ULN for serum ALT and to identify factors modulating it. SUBJECTS AND METHODS: We reviewed medical records of subjects aged 15-90, who underwent standard panels of laboratory tests, including serum ALT, over 6 months at a central laboratory. Three groups were defined: Group 1, comprised total study population (N=272 273). Group 2 (N=87 020) comprised total study population, excluding those receiving potentially hepatotoxic drugs, or diagnosed with liver disease, or had any abnormal laboratory test results other than for triglycerides, cholesterol, glucose, or HbA1c. Group 3 (N=17 496) the 'healthy' population, from whose ALT values we established the new ULN, comprised Group 2 subjects with normal triglycerides, cholesterol, glucose, and HbA1c levels. RESULTS: The 95th percentile ALT values, corresponding to the ULN, in groups 1, 2, and 3 were 50.1, 40, and 37.5 U/l, respectively. 6.2% (16 943/273 273) of subjects whose ALT was below ULN listed by the test manufacturer (52 U/l), had ALT level above our new ULN. Linear and logistic-regression analyses showed that ALT levels were significantly modified by gender, age, glucose, cholesterol, triglycerides, and overweight/obesity diagnosis. Significant interaction was found between gender, glucose and cholesterol levels. CONCLUSIONS: In this first large-scale study of 'healthy' population, serum ALT ULN was far lower than currently accepted value. Age and gender may be considered when determining the ULN for ALT. 相似文献
25.
E Jung L O Zamir R A Jensen 《Proceedings of the National Academy of Sciences of the United States of America》1986,83(19):7231-7235
The specific enzymological route of L-phenylalanine biosynthesis has not been established in any higher plant system. The possible pathway routes that have been identified in microorganisms utilize either phenylpyruvate or L-arogenate as a unique intermediate. We now report the presence of arogenate dehydratase (which converts L-arogenate to L-phenylalanine) in cultured-cell populations of Nicotiana silvestris. Prephenate dehydratase (which converts prephenate to phenylpyruvate) was not detected. Arogenate dehydratase was also found in washed spinach chloroplasts, and these data add to emerging evidence in support of the existence in the plastidial compartment of a complete assembly of enzymes comprising aromatic amino acid biosynthesis. Arogenate dehydratase from tobacco and spinach were both specific for L-arogenate, inhibited by L-phenylalanine, and activated by L-tyrosine. Apparent Km values for L-arogenate (0.3 X 10(-3) M), pH optima (pH 8.5-9.5), and temperature optima for catalysis (32-34 degrees C) were also similar. 相似文献
26.
27.
Nakhleh N Francis R Giese RA Tian X Li Y Zariwala MA Yagi H Khalifa O Kureshi S Chatterjee B Sabol SL Swisher M Connelly PS Daniels MP Srinivasan A Kuehl K Kravitz N Burns K Sami I Omran H Barmada M Olivier K Chawla KK Leigh M Jonas R Knowles M Leatherbury L Lo CW 《Circulation》2012,125(18):2232-2242
28.
Joan S. Baizer Nadav Weinstock Sandra F. Witelson Chet C. Sherwood Patrick R. Hof 《Brain structure & function》2013,218(2):389-403
The human cerebral cortex and cerebellum are greatly expanded compared to those of other mammals, including the great apes. This expansion is reflected in differences in the size and organization of precerebellar brainstem structures, such as the inferior olive. In addition, there are cell groups unique to the human brainstem. One such group may be the nucleus pararaphales (PRa); however, there is disagreement among authors about the size and location of this nucleus in the human brainstem. The name “pararaphales” has also been used for neurons in the medulla shown to project to the flocculus in the macaque monkey. We have re-examined the existence and status of the PRa in eight humans, three chimpanzees, and four macaque monkeys using Nissl-stained sections as well as immunohistochemistry. In the human we found a cell group along the midline of the medulla in all cases; it had the form of interrupted cell columns and was variable among cases in rostrocaudal and dorsoventral extent. Cells and processes were highly immunoreactive for non-phosphorylated neurofilament protein (NPNFP); somata were immunoreactive to the synthetic enzyme for nitric oxide, nitric oxide synthase, and for calretinin. In macaque monkey, there was a much smaller oval cell group with NPNFP immunoreactivity. In the chimpanzee, we found a region of NPNFP-immunoreactive cells and fibers similar to what was observed in macaques. These results suggest that the “PRa” in the human may not be the same structure as the flocculus-projecting cell group described in the macaque. The PRa, like the arcuate nucleus, therefore may be unique to humans. 相似文献
29.
30.