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Among the chief limitations in achieving early detection and control of animal‐origin influenza of pandemic potential in high‐risk livestock populations is the existing lag time between sample collection and diagnostic result. Advances in molecular diagnostics are permitting deployment of affordable, rapid, highly sensitive, and specific point‐of‐capture assays, providing opportunities for targeted surveillance driving containment strategies with potentially compelling returns on investment. Interrupting disease transmission at source holds promise of disrupting cycles of animal‐origin influenza incursion to endemicity and limiting impact on animal production, food security, and public health. Adoption of new point‐of‐capture diagnostics should be undertaken in the context of promoting robust veterinary services systems and parallel support for operationalizing pre‐authorized plans and communication strategies that will ensure that the full potential of these new platforms is realized.  相似文献   
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IntroductionThe free radial forearm (FRFA) flap is universally still considered as the gold standard technique in penile reconstruction. Typically, a considerably large flap is required, often involving almost the entire circumference of the forearm. Partial necrosis may occur at the distal-most (dorsoradial) part of the flap as a result of insufficient perfusion.AimTo describe a new technique using the posterior interosseous artery (PIOA) to supercharge FRFA phalloplasty.MethodsIn a 12-month period, all patients having FRFA flap phalloplasty were enrolled. Perioperative, after complete flap dissection, an indocyanine green perfusion scan was performed. In case of insufficient perfusion at the distalmost part of the flap, a supramicrosurgical anastomosis was performed between the FRFA pedicle and the PIOA (artery only).Main Outcome MeasuresStudied outcomes included the rate of marginal necrosis, surgical time, postoperative posterior interosseous nerve damage and urethral complications (fistula, stenosis or necrosis).ResultsA total of 27 FRFA flap phalloplasties was performed. Anastomosis of the PIOA was needed in 15 cases. No marginal necrosis was observed in these cases. There were no cases of postoperative posterior interosseous nerve damage. There were no significant differences in urethral complications (fistula, stenosis or necrosis) between the 2 groups.Clinical ImplicationsIn selected cases where insufficient perfusion of the dorsoradial part of the flap is present, patients may benefit from arterial supercharging to prevent postoperative marginal necrosis.Strength & LimitationsStrengths include a single surgeon, thus lending continuity of skill and technique, a consecutive series, and 100% short-term follow-up. Limitations include single institution series and a limited number of patients.ConclusionArterial supercharging is effective in improving perfusion of large FRFA flaps used in phalloplasty when dorsoradial hypoperfusion is detected on an indocyanine green perfusion scan. It is a technically challenging addition to the standard technique because of the small size of the vessels, the close relationship between the PIOA and the posterior interosseous nerve, and the vulnerability of the newly constructed intra-flap anastomosis.De Wolf E, Claes K, Sommeling CE, et al. Free Bipedicled Radial Forearm and Posterior Interosseous Artery Perforator Flap Phalloplasty. J Sex Med 2019;16:1111–1117.  相似文献   
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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.47 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.

Table 1

Demographic, clinical, and laboratory findings
CasesSexAge (years)Geographic regionPresenting symptomsInitial treatment before appearance of subcutaneous nodulesMorphology and location of subcutaneous nodulesRegional lymphadenopathyInvestigationsTreatment with intravenous sodium stibogluconateResponse to treatment
1M16Negev Desert8-month history of an infiltrated and ulcerated erythematous plaque on right forearmParomomycin ointmentSubcutaneous painless cord extending proximally in a linear pattern from the right antecubital fossa toward the axilla (Figure 1A, ,BB)NoSmear: positive for amastigotesYesFlattening of the indurated plaque and disappearance of the subcutaneous cord
Doppler ultrasound: infiltration of lymphatic vessels
2M1.8Negev Desert6-month history of an ulcerated erythematous plaque on the right lower foreheadParomomycin ointment and intralesional sodium stibogluconateTwo 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 stibogluconateYes (cervical)Smear: positive for amastigotesNoSubcutaneous nodules spontaneously regressed and the ulcerated plaque healed leaving a scar
Ultrasound: nondiagnostic
3F16Judean Desert1-year history of two ulcerated erythematous plaques on right and left forearmsParomomycin ointment and four treatment with intralesional sodium stibogluconate once weeklyNumerous 2-mm subcutaneous nodules above the primary lesions up to the armpit in both upper extremitiesYes (axillary)Smear: positive for amastigotesYesFlattening 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
4M9Judean Desert10-month history of infiltrated erythematous, ulcerated plaques on the right cheek, right upper lip, angle of mouth, and left forearmTwo intralesional treatments with sodium stibogluconateSubcutaneous cord extending from the right angle of the mouth to the right aspect of the jaw (Figure 3A)NoSmear: positive for amastigotesYesResolution 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
5F7Judean Desert2 months history of erosive erythematous plaques at the tip of the nose, upper lip and five papules on right armThree intralesional treatments with sodium stibogluconateTwo subcutaneous nodules, without overlying erythema, proximal to the nose lesionNoSmear: positive for amastigotesNoContinued 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
6M17Judean Desert3 months history of an ulcerated plaque on the middle phalanx of the fourth finger and an erythematous erosive plaque on right upper armOne intralesional treatment with sodium stibogluconateTwo subcutaneous nodules on the dorsal aspect of the right hand, proximal to the lesion on fourth finger (Figure 3C, ,DD)NoBiopsy (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 areasNoContinued 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
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   
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During pregnancy, women with polycystic ovary syndrome (PCOS) display high circulating androgen levels that may affect the fetus and increase the risk of mood disorders in offspring. This study investigated whether maternal androgen excess causes anxiety-like behavior in offspring mimicking anxiety disorders in PCOS. The PCOS phenotype was induced in rats following prenatal androgen (PNA) exposure. PNA offspring displayed anxiety-like behavior in the elevated plus maze, which was reversed by flutamide [androgen receptor (AR) blocker] and tamoxifen [selective estrogen receptor (ER) modulator]. Circulating sex steroids did not differ between groups at adult age. The expression of serotonergic and GABAergic genes associated with emotional regulation in the amygdala was consistent with anxiety-like behavior in female, and partly in male PNA offspring. Furthermore, AR expression in amygdala was reduced in female PNA offspring and also in females exposed to testosterone in adult age. To determine whether AR activation in amygdala affects anxiety-like behavior, female rats were given testosterone microinjections into amygdala, which resulted in anxiety-like behavior. Together, these data describe the anxiety-like behavior in PNA offspring and adult females with androgen excess, an impact that seems to occur during fetal life, and is mediated via AR in amygdala, together with changes in ERα, serotonergic, and GABAergic genes in amygdala and hippocampus. The anxiety-like behavior following testosterone microinjections into amygdala demonstrates a key role for AR activation in this brain area. These results suggest that maternal androgen excess may underpin the risk of developing anxiety disorders in daughters and sons of PCOS mothers.Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by excessive androgen secretion and abnormal insulin activity and affects up to 17% of women worldwide (1). Women with PCOS are at an increased risk of developing symptoms of anxiety and depression. In fact, over 60% of women with PCOS are diagnosed with at least one psychiatric disorder, such as depression, anxiety, or an eating disorder (2). Suicide attempts have also been shown to be seven times more common in women with PCOS than in healthy controls (3). The mechanisms underlying the development of PCOS are poorly understood. Although a genetic basis for PCOS has been suggested, the intrauterine milieu might also affect the reproductive/endocrine function of a child born to a PCOS mother in a manner that is independent of genetic inheritance or sex. It is also known that daughters of mothers with PCOS are at increased risk of developing the syndrome and that sons tend to suffer from obesity and insulin resistance (4). Thus, it has been proposed that PCOS originates during fetal development and that this might be, in part, a result of maternal androgen excess (5).Maternal testosterone levels in humans have been shown to affect brain morphology and function (6) and to be correlated to neural development and mental function (7). There is evidence for a crucial role of the hippocampus and the amygdala in the development of anxiety and depression, and that these neural circuits are affected by fluctuations in sex steroids in humans and in rodents (8). We have previously demonstrated that continuous exposure to dihydrotestosterone (DHT) from puberty until adulthood in female rats down-regulates androgen receptor (AR) expression in the hypothalamus and induces anxiety-like behavior in female rats (9). The increased rates of anxiety disorders and disruptive behavioral disorders among children with genetically induced hyperandrogenism further indicate that androgen excess may contribute to a higher risk of psychopathology (10).During pregnancy, androgens are metabolized to estrogens by the placenta in women and by the ovaries in rodents. Thus, the effects of testosterone on pregnancy are partly mediated by estrogen (11). Women with PCOS exhibit high circulating androgen levels during pregnancy, which hypothetically could be related to the increased risk of mood disorders in their offspring (12).Here, we tested the hypothesis that an excess of androgens in dams during pregnancy may cause anxiety-like behavior in adult female and male offspring. We used the prenatal androgen (PNA) model, which mimics the elevation of androgens in women with PCOS during pregnancy (13). The phenotype of the PNA model in mice (14) and in rats (12) reflects reproductive and metabolic characteristics of lean women with PCOS. However, whether it reflects symptoms of anxiety (2) is unknown. We demonstrated that female PNA offspring exhibited increased anxiety-like behavior, which was prevented by blocking the AR during pregnancy, implicating AR-mediated signaling in mediating the altered behavior of PNA offspring. To understand the neuroanatomical distribution of sites affected by the PNA treatment we evaluated the gene expression of key steroid receptors [Ar, estrogen receptor-α (Erα), Erβ, and G protein-coupled estrogen receptor (Gper)] in the hypothalamus, hippocampus, and amygdala, brain areas known to be involved in the regulation of mood behavior in female offspring. The expression of the AR gene was selectively altered in the amygdala of the PNA offspring. We further show that subchronic testosterone exposure in adult females also reduced Ar expression in the amygdala. Because the amygdala is known to be involved in the regulation of mood behavior, we hypothesized that testosterone exerts an anxiogenic effect in the amygdala. We obtained support for this hypothesis by demonstrating that intra-amygdala testosterone microinjections resulted in anxiety-like behavior.  相似文献   
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Background: The facial region has traditionally been quantified using linear anthropometrics. These are well established in dentistry, but require expertise to be used effectively. The aim of this study was to augment the utility of linear anthropometrics by applying them in conjunction with modern 3‐D morphometrics. Methods: Facial images of 75 males and 94 females aged 18–25 years with self‐reported Caucasian ancestry were used. An anthropometric mask was applied to establish corresponding quasi‐landmarks on the images in the dataset. A statistical face‐space, encoding shape covariation, was established. The facial median plane was extracted facilitating both manual and automated indication of commonly used midline landmarks. From both indications, facial convexity angles were calculated and compared. The angles were related to the face‐space using a regression based pathway enabling the visualization of facial form associated with convexity variation. Results: Good agreement between the manual and automated angles was found (Pearson correlation: 0.9478–0.9474, Dahlberg root mean squared error: 1.15°–1.24°). The population mean angle was 166.59°–166.29° (SD 5.09°–5.2°) for males–females. The angle‐pathway provided valuable feedback. Conclusions: Linear facial anthropometrics can be extended when used in combination with a face‐space derived from 3‐D scans and the exploration of property pathways inferred in a statistically verifiable way.  相似文献   
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Background

This level IV study describes a new one-stage procedure for revision ACL reconstruction in cases with extreme tunnel widening.

Methods

Eight consecutively treated subjects requiring ACL revision and presenting with excessive tunnel widening (87.5% to 250% tunnel enlargement) were included in this study. The graft-tunnel mismatch was resolved in this one-stage revision procedure by the use of custom-made eight to 10?mm cylindrical shaped bone allografts in a press-fit construct with the ACL-graft in combination with the usual fixation devices for ACL-reconstruction. All subjects were evaluated pre-operatively and at a minimum follow-up of one year by the IKDC objective and subjective scores, KOOS, and Tegner activity scale.

Results

Mean improvement was 24.8?±?16.1 on the KOOS evaluation (P-value 0,006) and 38.1?±?16.8 on the IKDC subjective score (P-value 0,001). The objective IKDC scores improved significantly with an average of one grade (P-value 0,038). Anterior laxity as determined on the KT-1000 arthrometer improved with an average of 3.63?mm compared to the situation before primary reconstruction, and the Pivot-shift test was negative in all but one patient after the revision procedure while positive in all patients before primary reconstruction.

Conclusion

This new surgical technique using eight to 10?mm allograft bone cylinders for the management of excessive tunnel enlargement at single stage revision ACL reconstruction delivers excellent results after minimum one year of follow-up. The results of this study have the potential to lower the threshold for one-stage surgery in ACL revision complicated by extreme tunnel widening.  相似文献   
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